Methods for Treating HCV

ABSTRACT

The present invention features interferon-free therapies for the treatment of HCV. Preferably, the treatment is over a shorter duration of treatment, such as no more than 12 weeks. In one aspect, the treatment comprises administering at least two direct acting antiviral agents to a subject with HCV infection, wherein the treatment lasts for 12 weeks and does not include administration of either interferon or ribavirin, and said at least two direct acting antiviral agents comprise (a) Compound 1 or a pharmaceutically acceptable salt thereof and (b) Compound 2 or a pharmaceutically acceptable salt thereof.

FIELD OF THE INVENTION

The present invention relates to interferon- and ribavirin-freetreatment for hepatitis C virus (HCV).

BACKGROUND OF THE INVENTION

The HCV is an RNA virus belonging to the Hepacivirus genus in theFlaviviridae family. The enveloped HCV virion contains a positivestranded RNA genome encoding all known virus-specific proteins in asingle, uninterrupted, open reading frame. The open reading framecomprises approximately 9500 nucleotides and encodes a single largepolyprotein of about 3000 amino acids. The polyprotein comprises a coreprotein, envelope proteins E1 and E2, a membrane bound protein p7, andthe non-structural proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B.

Chronic HCV infection is associated with progressive liver pathology,including cirrhosis and hepatocellular carcinoma. Chronic hepatitis Cmay be treated with peginterferon-alpha in combination with ribavirin.Substantial limitations to efficacy and tolerability remain as manyusers suffer from side effects, and viral elimination from the body isoften incomplete. Therefore, there is a need for new therapies to treatHCV infection.

BRIEF SUMMARY OF THE INVENTION

One aspect of the present invention features methods for treating HCVinfection in a subject in need of such treatment. The methods compriseadministering at least two direct acting antiviral agents (DAAs) to thesubject for a duration of no more than 12 weeks, or for another durationas set forth herein. The at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof); and the at least two DAAs canalso additionally comprise one or more other DAAs, such as sofosbuvir oranother HCV polymerase inhibitor. Preferably, the duration of thetreatment is 12 weeks. The duration of the treatment can also last forless than 12 weeks; for example, the duration can last for 11, 10, 9, 8,7, 6, 5 or 4 weeks, or no more than 8 weeks. Where three or more DAAsare used in the treatment regimen, the duration of the treatmentpreferably lasts for no more than 8 weeks; for example, the duration canlast for 8, 7, 6, 5 or 4 weeks. Preferably, the two or more DAAs areadministered in amounts effective to provide a sustained virologicalresponse (SVR) or achieve another desired measure of effectiveness inthe subject. The subject is not administered either interferon orribavirin during the treatment regimen. Put another way, the methodsexclude the administration of interferon and ribavirin to the subject,thereby avoiding the side effects associated with interferon orribavirin.

Another aspect of the present invention features methods for treating apopulation of subjects having HCV infection. The methods compriseadministering at least two DAAs to the subjects for a duration of nomore than 12 weeks, such as for a duration of 12, 11, 10, 9, 8, 7, 6, 5or 4 weeks, or no more than 8 weeks. The at least two DAAs compriseCompound 1 (or a pharmaceutically acceptable salt thereof) and Compound2 (or a pharmaceutically acceptable salt thereof); and the at least twoDAAs can also additionally comprise one or more other DAAs, such assofosbuvir or another HCV polymerase inhibitor. Preferably, the at leasttwo DAAs are administered to the subjects in amounts effective to resultin SVR or another measure of effectiveness in at least about 70% of thepopulation, preferably at least about 80% of the population, or morepreferably at least about 90% of the population.

In any method described herein, the at least two DAAs comprise (a)Compound 1 or a pharmaceutically acceptable salt thereof, and (b)Compound 2 or a pharmaceutically acceptable salt thereof. The at leasttwo DAAs can also optionally comprise one or more other anti-HCV agents.These other optional anti-HCV agents can be selected from proteaseinhibitors, nucleoside or nucleotide polymerase inhibitors,non-nucleoside polymerase inhibitors, NS3B inhibitors, NS4A inhibitors,NS5A inhibitors, NS5B inhibitors, cyclophilin inhibitors, orcombinations thereof. Non-limiting examples of the other optionalantic-HCV agents include PSI-7977 (sofosbuvir), PSI-938, BMS-790052(daclatasvir), BMS-650032 (asunaprevir), BMS-791325, GS-5885(ledipasvir), GS-9451 (tegobuvir), GS-9190, GS-9256, BI-201335,BI-27127, telaprevir, VX-222, TMC-435 (simepravir), MK-5172, MK-7009(vaniprevir), danoprevir, R7128 (mericitabine), and any combinationthereof.

For example, the DAAs used in a method of the present invention cancomprise or consist of (a) Compound 1 or a pharmaceutically acceptablesalt thereof, and (b) Compound 2 or a pharmaceutically acceptable saltthereof. For another example, the DAAs used in a method of the presentinvention can comprise or consist of (a) Compound 1 or apharmaceutically acceptable salt thereof, (b) Compound 2 or apharmaceutically acceptable salt thereof, and (c) a HCV polymeraseinhibitor, wherein said HCV polymerase inhibitor can be a nucleotide ornucleoside polymerase inhibitor or a non-nucleoside or non-nucleotidepolymerase inhibitor. For yet another example, the DAAs used in a methodof the present invention can comprise or consist of (a) Compound 1 or apharmaceutically acceptable salt thereof, (b) Compound 2 or apharmaceutically acceptable salt thereof, and (c) a nucleotide ornucleoside HCV polymerase inhibitor. For yet another example, the DAAsused in a method of the present invention can comprise or consist of (a)Compound 1 or a pharmaceutically acceptable salt thereof, (b) Compound 2or a pharmaceutically acceptable salt thereof, and (c) sofosbuvir. Foryet another example, the DAAs used in a method of the present inventioncan comprise or consist of (a) Compound 2 or a pharmaceuticallyacceptable salt thereof and (b) sofosbuvir.

In any method described herein, the DAAs can be administered in anyeffective dosing schemes and/or frequencies; for example, they can eachbe administered daily. Each DAA can be administered either separately orin combination, and each DAA can be administered once a day, twice aday, or three times a day. Preferably, Compound 1 (or a pharmaceuticallyacceptable salt thereof) and Compound 2 (or a pharmaceuticallyacceptable salt thereof) are administered once daily (QD).

Preferably, Compound 1 (or a pharmaceutically acceptable salt thereof)is administered from 100 mg to 600 mg once daily, and Compound 2 (or apharmaceutically acceptable salt thereof) is administered from 50 to 500mg once daily. More preferably, Compound 1 (or a pharmaceuticallyacceptable salt thereof) is administered from 200 mg to 600 mg oncedaily, and Compound 2 (or a pharmaceutically acceptable salt thereof) isadministered from 100 to 500 mg once daily. Highly preferably, Compound1 (or a pharmaceutically acceptable salt thereof) is administered from400 mg to 600 mg once daily, and Compound 2 (or a pharmaceuticallyacceptable salt thereof) is administered from 100 to 500 mg once daily.It was unexpectedly found that 200-300 mg Compound 1 has comparableanti-HCV efficacy to 400 mg Compound 1. Therefore, more preferably,Compound 1 (or a pharmaceutically acceptable salt thereof) isadministered from 200 mg to 300 mg once daily, and Compound 2 (or apharmaceutically acceptable salt thereof) is administered from 100 to500 mg once daily. For example, Compound 1 (or a pharmaceuticallyacceptable salt thereof) can be administered 200 mg once daily, andCompound 2 (or a pharmaceutically acceptable salt thereof) isadministered 120 mg once daily. For another example, Compound 1 (or apharmaceutically acceptable salt thereof) can be administered 300 mgonce daily, and Compound 2 (or a pharmaceutically acceptable saltthereof) is administered 120 mg once daily. For yet another example,Compound 1 (or a pharmaceutically acceptable salt thereof) can beadministered 400 mg once daily, and Compound 2 (or a pharmaceuticallyacceptable salt thereof) is administered 120 mg once daily. For anotherexample, Compound 1 (or a pharmaceutically acceptable salt thereof) canbe administered 400 mg once daily, and Compound 2 (or a pharmaceuticallyacceptable salt thereof) can be administered 240 mg once daily.

In yet another aspect, the present invention features a combination ofCompound 1 (or a pharmaceutically acceptable salt thereof) and Compound2 (or a pharmaceutically acceptable salt thereof) for use to treat HCVinfection. The treatment comprises administering the DAAs to a subjectinfected with HCV. The duration of the treatment regimen is no more thantwelve weeks (e.g., the duration being 12 weeks; or the duration being11, 10, 9, 8, 7, 6, 5, 4, or 3 weeks). Preferably, the duration of thetreatment regimen is twelve weeks. The duration of the treatment canalso last, for example, no more than eight weeks (e.g., the durationbeing 8 weeks; or the duration being 7, 6, 5, 4, or 3 weeks). Thetreatment does not include administering interferon or ribavirin (i.e.,neither interferon nor ribavirin are administered). Compound 1 (or thesalt thereof) and Compound 2 (or the salt thereof) can be administeredconcurrently or sequentially. Preferably, Compound 1 (or the saltthereof) and Compound 2 (or the salt thereof) can be administered oncedaily. As a non-limiting example, the patient being treated is infectedwith HCV genotype 1, such as genotype 1a or 1b. As another non-limitingexample, the patient is infected with HCV genotype 2. As anothernon-limiting example, the patient is infected with HCV genotype 3. Asanother non-limiting example, the patient is infected with HCV genotype4. As another non-limiting example, the patient is infected with HCVgenotype 5. As another non-limiting example, the patient is infectedwith HCV genotype 6. As yet another non-limiting example, the patient isa HCV-treatment naïve patient, a HCV-treatment experienced patient, aninterferon non-responder (e.g., a null responder), or not a candidatefor interferon treatment. As used in this application, the interferonnon-responder patients include partial interferon responders andinterferon rebound patients. See GUIDANCE FOR INDUSTRY—CHRONIC HEPATITISC VIRUS INFECTION: DEVELOPING DIRECT-ACTING ANTIVIRAL AGENTS FORTREATMENT (FDA, September 2010, draft guidance) for the definitions ofnaïve, partial responder, responder relapser (i.e., rebound), and nullresponder patients. The interferon non-responder patients also includenull responder patients. In one example of this aspect of the invention,the treatment lasts for 12 weeks, and the subject being treated is anaïve patient infected with HCV genotype 1. In another example, thetreatment lasts for 11 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In still another example, thetreatment lasts for 10 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 8 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 7 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 5 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 4 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 3. In another example, the treatmentlasts for 11 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In still another example, the treatmentlasts for 10 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 9 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 8 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 7 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 6 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 5 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 4 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 12 weeks, and the subject being treated is a non-responder(e.g., a null responder) infected with HCV genotype 1. In anotherexample, the treatment lasts for 11 weeks, and the subject being treatedis a non-responder (e.g., a null responder) infected with HCVgenotype 1. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inanother example, the treatment lasts for 11 weeks, and the subject beingtreated is a non-responder (e.g., a null responder) infected with HCVgenotype 3. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3.

In yet another aspect, the present invention features a combination ofCompound 1 (or a pharmaceutically acceptable salt thereof), Compound 2(or a pharmaceutically acceptable salt thereof), and an HCV polymeraseinhibitor for use to treat HCV infection. The treatment comprisesadministering the DAAs to a subject infected with HCV. The duration ofthe treatment regimen is no more than twelve weeks (e.g., the durationbeing 12 weeks; or the duration being 11, 10, 9, 8, 7, 6, 5, 4, or 3weeks). Preferably, the duration of the treatment regimen is twelveweeks. The duration of the treatment can also last, for example, no morethan eight weeks (e.g., the duration being 8 weeks; or the durationbeing 7, 6, 5, 4, or 3 weeks). The treatment does not includeadministering either interferon or ribavirin, i.e., neither interferonnor ribavirin are administered. Compound 1 (or the salt thereof),Compound 2 (or the salt thereof) and the HCV polymerase inhibitor can beadministered concurrently or sequentially. Preferably, Compound 1 (orthe salt thereof), Compound 2 (or the salt thereof) and the HCVpolymerase inhibitor can be administered once daily. As a non-limitingexample, the patient being treated is infected with HCV genotype 1, suchas genotype 1a or 1b. As another non-limiting example, the patient isinfected with HCV genotype 2. As another non-limiting example, thepatient is infected with HCV genotype 3. As another non-limitingexample, the patient is infected with HCV genotype 4. As anothernon-limiting example, the patient is infected with HCV genotype 5. Asanother non-limiting example, the patient is infected with HCV genotype6. As yet another non-limiting example, the patient is a HCV-treatmentnaïve patient, a HCV-treatment experienced patient, an interferonnon-responder (e.g., a null responder), or not a candidate forinterferon treatment. In one example of this aspect of the invention,the treatment lasts for 12 weeks, and the subject being treated is anaïve patient infected with HCV genotype 1. In another example, thetreatment lasts for 11 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In still another example, thetreatment lasts for 10 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 8 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 7 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 5 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 4 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 3. In another example, the treatmentlasts for 11 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In still another example, the treatmentlasts for 10 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 9 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 8 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 7 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 6 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 5 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 4 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 12 weeks, and the subject being treated is a non-responder(e.g., a null responder) infected with HCV genotype 1. In anotherexample, the treatment lasts for 11 weeks, and the subject being treatedis a non-responder (e.g., a null responder) infected with HCVgenotype 1. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inanother example, the treatment lasts for 11 weeks, and the subject beingtreated is a non-responder (e.g., a null responder) infected with HCVgenotype 3. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3.

In yet another aspect, the present invention features a combination ofCompound 1 (or a pharmaceutically acceptable salt thereof), Compound 2(or a pharmaceutically acceptable salt thereof), and sofosbuvir for useto treat HCV infection. The treatment comprises administering the DAAsto a subject infected with HCV. The duration of the treatment regimen isno more than twelve weeks (e.g., the duration being 12 weeks; or theduration being 11, 10, 9, 8, 7, 6, 5, 4, or 3 weeks). Preferably, theduration of the treatment regimen is twelve weeks. The duration of thetreatment can also last, for example, no more than eight weeks (e.g.,the duration being 8 weeks; or the duration being 7, 6, 5, 4, or 3weeks). The treatment does not include administering interferon.Compound 1 (or the salt thereof), Compound 2 (or the salt thereof) andsofosbuvir can be administered concurrently or sequentially. Preferably,Compound 1 (or the salt thereof), Compound 2 (or the salt thereof) andsofosbuvir can be administered once daily. As a non-limiting example,the patient being treated is infected with HCV genotype 1, such asgenotype 1a or 1b. As another non-limiting example, the patient isinfected with HCV genotype 2. As another non-limiting example, thepatient is infected with HCV genotype 3. As another non-limitingexample, the patient is infected with HCV genotype 4. As anothernon-limiting example, the patient is infected with HCV genotype 5. Asanother non-limiting example, the patient is infected with HCV genotype6. As yet another non-limiting example, the patient is a HCV-treatmentnaïve patient, a HCV-treatment experienced patient, an interferonnon-responder (e.g., a null responder), or not a candidate forinterferon treatment. In one example of this aspect of the invention,the treatment lasts for 12 weeks, and the subject being treated is anaïve patient infected with HCV genotype 1. In another example, thetreatment lasts for 11 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In still another example, thetreatment lasts for 10 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 8 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 7 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 5 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 4 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 3. In another example, the treatmentlasts for 11 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In still another example, the treatmentlasts for 10 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 9 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 8 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 7 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 6 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 5 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 4 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 12 weeks, and the subject being treated is a non-responder(e.g., a null responder) infected with HCV genotype 1. In anotherexample, the treatment lasts for 11 weeks, and the subject being treatedis a non-responder (e.g., a null responder) infected with HCVgenotype 1. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inanother example, the treatment lasts for 11 weeks, and the subject beingtreated is a non-responder (e.g., a null responder) infected with HCVgenotype 3. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3.

In yet another aspect, the present invention features a combination ofCompound 2 (or a pharmaceutically acceptable salt thereof) andsofosbuvir for use to treat HCV infection. The treatment comprisesadministering the DAAs to a subject infected with HCV. The duration ofthe treatment regimen is no more than twelve weeks (e.g., the durationbeing 12 weeks; or the duration being 11, 10, 9, 8, 7, 6, 5, 4, or 3weeks). Preferably, the duration of the treatment regimen is twelveweeks. The duration of the treatment can also last, for example, no morethan eight weeks (e.g., the duration being 8 weeks; or the durationbeing 7, 6, 5, 4, or 3 weeks). The treatment does not includeadministering interferon. Compound 2 (or the salt thereof) andsofosbuvir can be administered concurrently or sequentially. Preferably,Compound 2 (or the salt thereof) and sofosbuvir can be administered oncedaily. As a non-limiting example, the patient being treated is infectedwith HCV genotype 1, such as genotype 1a or 1b. As another non-limitingexample, the patient is infected with HCV genotype 2. As anothernon-limiting example, the patient is infected with HCV genotype 3. Asanother non-limiting example, the patient is infected with HCV genotype4. As another non-limiting example, the patient is infected with HCVgenotype 5. As another non-limiting example, the patient is infectedwith HCV genotype 6. As yet another non-limiting example, the patient isa HCV-treatment naïve patient, a HCV-treatment experienced patient, aninterferon non-responder (e.g., a null responder), or not a candidatefor interferon treatment. In one example of this aspect of theinvention, the treatment lasts for 12 weeks, and the subject beingtreated is a naïve patient infected with HCV genotype 1. In anotherexample, the treatment lasts for 11 weeks, and the subject being treatedis a naïve patient infected with HCV genotype 1. In still anotherexample, the treatment lasts for 10 weeks, and the subject being treatedis a naïve patient infected with HCV genotype 1. In yet another example,the treatment lasts for 9 weeks, and the subject being treated is anaïve patient infected with HCV genotype 1. In yet another example, thetreatment lasts for 8 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 7 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 5 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 4 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is a naïvepatient infected with HCV genotype 3. In another example, the treatmentlasts for 11 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In still another example, the treatmentlasts for 10 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 9 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 8 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 7 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 6 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 5 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 4 weeks, and the subject being treated is a naïve patientinfected with HCV genotype 3. In yet another example, the treatmentlasts for 12 weeks, and the subject being treated is a non-responder(e.g., a null responder) infected with HCV genotype 1. In anotherexample, the treatment lasts for 11 weeks, and the subject being treatedis a non-responder (e.g., a null responder) infected with HCVgenotype 1. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 1. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 1. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 1. In yet another example, thetreatment lasts for 12 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inanother example, the treatment lasts for 11 weeks, and the subject beingtreated is a non-responder (e.g., a null responder) infected with HCVgenotype 3. In still another example, the treatment lasts for 10 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 9 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 8 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 7 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3. In yet another example, thetreatment lasts for 6 weeks, and the subject being treated is anon-responder (e.g., a null responder) infected with HCV genotype 3. Inyet another example, the treatment lasts for 5 weeks, and the subjectbeing treated is a non-responder (e.g., a null responder) infected withHCV genotype 3. In yet another example, the treatment lasts for 4 weeks,and the subject being treated is a non-responder (e.g., a nullresponder) infected with HCV genotype 3.

A treatment regimen of the present invention generally constitutes acomplete treatment regimen, i.e., no subsequent interferon-containingregimen is intended. Thus, a treatment or use described herein generallydoes not include any subsequent interferon-containing orribavirin-containing treatment.

Other features, objects, and advantages of the present invention areapparent in the detailed description that follows. It should beunderstood, however, that the detailed description, while indicatingpreferred embodiments of the invention, are given by way of illustrationonly, not limitation. Various changes and modifications within the scopeof the invention will become apparent to those skilled in the art fromthe detailed description

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings are provided for illustration, not limitation.

FIG. 1 shows the predicted median SVR percentages and 90% SVR confidenceintervals for interferon/ribavirin-free, 2-DAA regimens comprising theuse of Compound 1 (400 mg once daily) and Compound 2 (120 mg once daily)to treat genotype 1 naïve subjects.

FIG. 2 illustrates the predicted median SVR percentages and 90% SVRconfidence intervals for interferon/ribavirin-free, 2-DAA regimenscomprising the use of Compound 1 (400 mg once daily) and Compound 2 (60mg once daily) to treat genotype 1 naïve subjects.

FIG. 3 depicts the predicted median SVR percentages and 90% SVRconfidence intervals for interferon/ribavirin-free, 2-DAA regimenscomprising the use of Compound 1 (600 mg once daily) and Compound 2 (480mg once daily) to treat genotype 1 naïve subjects.

FIG. 4 shows the predicted median SVR percentages and 90% SVR confidenceintervals for interferon/ribavirin-free, 2-DAA regimens comprising theuse of Compound 1 (400 mg once daily) and Compound 2 (120 mg once daily)to treat genotype 3 naïve subjects.

FIG. 5 illustrates the predicted median SVR percentages and 90% SVRconfidence intervals for interferon/ribavirin-free, 2-DAA regimenscomprising the use of Compound 1 (400 mg once daily) and Compound 2 (60mg once daily) to treat genotype 3 naïve subjects.

FIG. 6 shows the predicted median SVR percentages and 90% SVR confidenceintervals for interferon/ribavirin-free, 2-DAA regimens comprising theuse of Compound 1 (600 mg once daily) and Compound 2 (480 mg once daily)to treat genotype 3 naïve subjects.

FIG. 7 shows the predicted median SVR percentages and 90% SVR confidenceintervals for interferon/ribavirin-free, 3-DAA regimens comprising theuse of Compound 1 (400 mg once daily), Compound 2 (120 mg once daily)and sofosbuvir (400 mg once daily) to treat genotype 1 naïve subjects.

FIG. 8 shows the predicted median SVR percentages and 90% SVR confidenceintervals for interferon/ribavirin-free, 2-DAA regimens comprising theuse of Compound 2 (120 mg once daily) and sofosbuvir (400 mg once daily)to treat genotype 1 naïve subjects.

FIG. 9 depict the synergistic effect of the combination of Compound 1and Compound 2 on HCV inhibition in vitro.

DETAILED DESCRIPTION OF THE INVENTION

The methods of the present invention include administering Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof) to a subject in need thereof.Compound 1 has the following structure:

Compound 1 is a potent HCV protease inhibitor and is described in U.S.Patent Application Publication No. 2012/0070416.

Compound 2 has the following structure:

Compound 2 is a potent NS5A inhibitor and is described in U.S. PatentApplication Publication No. 2012/0220562.

The interferon/ribavirin-based treatment may be physically demanding,and can lead to temporary disability in some cases. A substantialproportion of patients will experience a panoply of side effects rangingfrom a “flu-like” syndrome (the most common, experienced for a few daysafter the weekly injection of interferon) to severe adverse eventsincluding anemia, cardiovascular events and psychiatric problems such assuicide or suicidal ideation. The latter are exacerbated by the generalphysiological stress experienced by the patients. Ribavirin also has anumber of side effects, including, anemia, high pill burden (e.g. 5-6pills a day split BID) and teratogenicity restricting use in women ofchildbearing age.

The methods of the present invention provide effective treatment of HCVinfection without the use of interferon or ribavirin and for a shorterperiod of time, for example and without limitation, a treatment durationof no more than twelve weeks, alternatively no more than eleven weeks,alternatively no more than ten weeks, alternatively no more than nineweeks, alternatively no more than eight weeks, alternatively no morethan seven weeks, alternatively no more than six weeks, alternatively nomore than five weeks, alternatively no more than four weeks, oralternatively, no more than three weeks.

In one aspect, the present invention features methods for treating HCVinfection in a subject comprising administering at least two DAAs, inthe absence of interferon and ribavirin, to the subject for a durationof no more than twelve weeks, alternatively no more than eight weeks,such as for a duration of 12, 11, 10, 9, 8, 7, 6, 5, or 4 weeks. Putanother way, the methods exclude interferon and ribavirin, i.e. neitherinterferon nor ribavirin are administered. The at least two DAAscomprise Compound 1 (or a pharmaceutically acceptable salt thereof) andCompound 2 (or a pharmaceutically acceptable salt thereof), which can beco-administered, or administered separately or independently, with thesame or different dosing frequencies. Preferably, the at least two DAAsare administered once a day. They can also be administered, for example,twice a day or three times a day.

In one aspect, the present invention features methods for treating HCVinfection in a subject comprising administering at least two DAAs, inthe absence of interferon and ribavirin, to the subject for a durationof no more than twelve weeks, alternatively no more than eight weeks,such as for a duration of 12, 11, 10, 9, 8, 7, 6, 5, or 4 weeks. Putanother way, the methods exclude interferon and ribavirin, i.e., neitherinterferon nor ribavirin are administered. The at least two DAAscomprise Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (or a pharmaceutically acceptable salt thereof) and an HCVpolymerase inhibitor, which can be co-administered, or administeredseparately or independently, with the same or different dosingfrequencies. Preferably, the at least two DAAs are administered once aday. They can also be administered, for example, twice a day or threetimes a day.

In one aspect, the present invention features methods for treating HCVinfection in a subject comprising administering at least two DAAs, inthe absence of interferon and ribavirin, to the subject for a durationof no more than twelve weeks, alternatively no more than eight weeks,such as for a duration of 12, 11, 10, 9, 8, 7, 6, 5, or 4 weeks. Putanother way, the methods exclude interferon and ribavirin, i.e., neitherinterferon nor ribavirin are administered. The at least two DAAscomprise Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (or a pharmaceutically acceptable salt thereof) andsofosbuvir, which can be co-administered, or administered separately orindependently, with the same or different dosing frequencies.Preferably, the at least two DAAs are administered once a day. They canalso be administered, for example, twice a day or three times a day.

In one aspect, the present invention features methods for treating HCVinfection in a subject comprising administering at least two DAAs, inthe absence of interferon and ribavirin, to the subject for a durationof no more than twelve weeks, alternatively no more than eight weeks,such as for a duration of 12, 11, 10, 9, 8, 7, 6, 5, or 4 weeks. Putanother way, the methods exclude interferon and ribavirin, i.e., neitherinterferon nor ribavirin are administered. The at least two DAAscomprise Compound 2 (or a pharmaceutically acceptable salt thereof) andsofosbuvir, which can be co-administered, or administered separately orindependently, with the same or different dosing frequencies.Preferably, the at least two DAAs are administered once a day. They canalso be administered, for example, twice a day or three times a day.

Various measures may be used to express the effectiveness of a method ofthe present invention. One such measure is SVR, which, as used herein,means that the virus is undetectable at the end of therapy and for atleast 8 weeks after the end of therapy (SVR8); preferably, the virus isundetectable at the end of therapy and for at least 12 weeks after theend of therapy (SVR12); more preferably, the virus is undetectable atthe end of therapy and for at least 16 weeks after the end of therapy(SVR16); and highly preferably, the virus is undetectable at the end oftherapy and for at least 24 weeks after the end of therapy (SVR24).SVR24 is often considered as a functional definition of cure; and a highrate of SVR at less than 24 week post-treatment (e.g., SVR8 or SVR12)can be predictive of a high rate of SVR24.

Preferably, a method described herein achieves at least 70% SVR8. Morepreferably, a method described herein achieves at least 80% SVR8. Highlypreferably, a method described herein achieves at least 90% SVR8. Mostpreferably, a method described herein achieves at least 95% SVR8.

Preferably, a method described herein achieves at least 70% SVR12. Morepreferably, a method described herein achieves at least 80% SVR12.Highly preferably, a method described herein achieves at least 90%SVR12. Most preferably, a method described herein achieves at least 95%SVR12. A method without achieving a significant SVR rate within patientsis not considered an effective treatment, despite the fact that othereffectiveness measures (e.g., RVR, eRVR, EVR, or ETR) may showsuppression of the HCV virus during the treatment or immediately at theend of the treatment.

In some embodiments, a treatment regimen of the invention comprisestreating a population of subjects having HCV infection (e.g. treatmentnaïve subjects), and the regimen comprises administering at least twoDAAs to the subjects for a duration of no more than 12 weeks, or foranother duration disclosed herein (e.g., 11, 10, 9, 8, 7, 6, 5, or 4weeks), wherein the at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof), and are administered to thesubjects in amounts effective to provide an SVR (e.g., SVR12 or SVR24)in at least about 70% of the population, alternatively at least about75% of the population, alternatively at least about 80% of thepopulation, alternatively at least about 85% of the population,alternatively at least about 90% of the population, alternatively atleast about 95% of the population, alternatively about 100% of thepopulation. In some embodiments, a treatment regimen of the inventioncomprises treating a population of IFN experienced subjects (e.g.,interferon non-responders) having HCV infection, and the methodcomprises administering at least two DAAs to the subjects for a durationof no more than 12 weeks, or for another duration disclosed herein,wherein the at least two DAAs comprise Compound 1 (or a pharmaceuticallyacceptable salt thereof) and Compound 2 (or a pharmaceuticallyacceptable salt thereof), and are administered to the subjects inamounts effective to provide an SVR (e.g., SVR12 or SVR24) in at leastabout 50% of the population, alternatively at least about 55% of thepopulation, alternatively at least about 60% of the population,alternatively at least about 65% of the population, alternatively atleast about 70% of the population, alternatively at least about 75% ofthe population, alternatively at least about 80% of the population,alternatively at least about 85% of the population, alternatively atleast about 90% of the population, alternatively at least about 95% ofthe population, or alternatively about 100% of the population.

In some embodiments, a treatment regimen of the invention comprisestreating a population of subjects having HCV infection (e.g. treatmentnaïve subjects), and the regimen comprises administering at least twoDAAs to the subjects for a duration of no more than 12 weeks, or foranother duration disclosed herein (e.g., 11, 10, 9, 8, 7, 6, 5, or 4weeks), wherein the at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor, and are administered to the subjects in amounts effective toprovide an SVR (e.g., SVR12 or SVR24) in at least about 70% of thepopulation, alternatively at least about 75% of the population,alternatively at least about 80% of the population, alternatively atleast about 85% of the population, alternatively at least about 90% ofthe population, alternatively at least about 95% of the population,alternatively about 100% of the population. In some embodiments, atreatment regimen of the invention comprises treating a population ofIFN experienced subjects (e.g., interferon non-responders) having HCVinfection, and the method comprises administering at least two DAAs tothe subjects for a duration of no more than 12 weeks, or for anotherduration disclosed herein, wherein the at least two DAAs compriseCompound 1 (or a pharmaceutically acceptable salt thereof), Compound 2(or a pharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor, and are administered to the subjects in amounts effective toprovide an SVR (e.g., SVR12 or SVR24) in at least about 50% of thepopulation, alternatively at least about 55% of the population,alternatively at least about 60% of the population, alternatively atleast about 65% of the population, alternatively at least about 70% ofthe population, alternatively at least about 75% of the population,alternatively at least about 80% of the population, alternatively atleast about 85% of the population, alternatively at least about 90% ofthe population, alternatively at least about 95% of the population, oralternatively about 100% of the population.

In some embodiments, a treatment regimen of the invention comprisestreating a population of subjects having HCV infection (e.g. treatmentnaïve subjects), and the regimen comprises administering at least twoDAAs to the subjects for a duration of no more than 12 weeks, or foranother duration disclosed herein (e.g., 11, 10, 9, 8, 7, 6, 5, or 4weeks), wherein the at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir, and areadministered to the subjects in amounts effective to provide an SVR(e.g., SVR12 or SVR24) in at least about 70% of the population,alternatively at least about 75% of the population, alternatively atleast about 80% of the population, alternatively at least about 85% ofthe population, alternatively at least about 90% of the population,alternatively at least about 95% of the population, alternatively about100% of the population. In some embodiments, a treatment regimen of theinvention comprises treating a population of IFN experienced subjects(e.g., interferon non-responders) having HCV infection, and the methodcomprises administering at least two DAAs to the subjects for a durationof no more than 12 weeks, or for another duration disclosed herein,wherein the at least two DAAs comprise Compound 1 (or a pharmaceuticallyacceptable salt thereof), Compound 2 (or a pharmaceutically acceptablesalt thereof) and sofosbuvir, and are administered to the subjects inamounts effective to provide an SVR (e.g., SVR12 or SVR24) in at leastabout 50% of the population, alternatively at least about 55% of thepopulation, alternatively at least about 60% of the population,alternatively at least about 65% of the population, alternatively atleast about 70% of the population, alternatively at least about 75% ofthe population, alternatively at least about 80% of the population,alternatively at least about 85% of the population, alternatively atleast about 90% of the population, alternatively at least about 95% ofthe population, or alternatively about 100% of the population.

In some embodiments, a treatment regimen of the invention comprisestreating a population of subjects having HCV infection (e.g. treatmentnaïve subjects), and the regimen comprises administering at least twoDAAs to the subjects for a duration of no more than 12 weeks, or foranother duration disclosed herein (e.g., 11, 10, 9, 8, 7, 6, 5, or 4weeks), wherein the at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir, and areadministered to the subjects in amounts effective to provide an SVR(e.g., SVR12 or SVR24) in at least about 70% of the population,alternatively at least about 75% of the population, alternatively atleast about 80% of the population, alternatively at least about 85% ofthe population, alternatively at least about 90% of the population,alternatively at least about 95% of the population, alternatively about100% of the population. In some embodiments, a treatment regimen of theinvention comprises treating a population of IFN experienced subjects(e.g., interferon non-responders) having HCV infection, and the methodcomprises administering at least two DAAs to the subjects for a durationof no more than 12 weeks, or for another duration disclosed herein,wherein the at least two DAAs comprise Compound 2 (or a pharmaceuticallyacceptable salt thereof) and sofosbuvir, and are administered to thesubjects in amounts effective to provide an SVR (e.g., SVR12 or SVR24)in at least about 50% of the population, alternatively at least about55% of the population, alternatively at least about 60% of thepopulation, alternatively at least about 65% of the population,alternatively at least about 70% of the population, alternatively atleast about 75% of the population, alternatively at least about 80% ofthe population, alternatively at least about 85% of the population,alternatively at least about 90% of the population, alternatively atleast about 95% of the population, or alternatively about 100% of thepopulation.

It was unexpected that an interferon-free treatment using a combinationof Compound 1 (or a pharmaceutically acceptable salt thereof) andCompound 2 (or a pharmaceutically acceptable salt thereof), in theabsence of interferon and ribavirin, and for a duration of no more than12 weeks, can achieve significant SVR.

Accordingly, in one aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 8 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In another aspect, the present invention features a method of treatingHCV infection, comprising administering to a patient in need thereof aneffective amount of a combination of at least two DAAs, wherein said atleast two DAAs comprise Compound 1 (or a pharmaceutically acceptablesalt thereof) and Compound 2 (or a pharmaceutically acceptable saltthereof). The treatment lasts 7 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 6 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 5 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 4 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 3 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 24 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 13 to 23weeks (e.g., the duration of the treatment is selected from 13, 14, 15,16, 17, 18, 19, 20, 21, 22 or 23 weeks) and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 12 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

As used in this application, an HCV polymerase inhibitor can be anucleoside polymerase inhibitor, a nucleotide polymerase inhibitor, anon-nucleoside polymerase inhibitor, or a non-nucleotide polymeraseinhibitor.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 11 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 10 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). The treatment lasts 9 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof) and Compound 2 (or a salt thereof), said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-7977, PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In another aspect, the present invention features a method of treatingHCV infection, comprising administering to a patient in need thereof aneffective amount of a combination of at least two DAAs, wherein said atleast two DAAs comprise Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (or a pharmaceutically acceptable saltthereof) and an HCV polymerase inhibitor. The treatment lasts 8 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In another aspect, the present invention features a method of treatingHCV infection, comprising administering to a patient in need thereof aneffective amount of a combination of at least two DAAs, wherein said atleast two DAAs comprise Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (or a pharmaceutically acceptable saltthereof) and an HCV polymerase inhibitor. The treatment lasts 7 weeksand does not include administration of any interferon or ribavirin(i.e., neither interferon nor ribavirin are administered). The DAAs canbe administered at the same or different dosing frequencies. The patientbeing treated can be a treatment naïve patient; a treatment experiencedpatient, including, but not limited to, a relapser, an interferonpartial responder, an interferon non-responder, or a null responder; ora patient unable to take interferon. The patient may be infected with,for example and without limitation, HCV genotype 1, such as HCV genotype1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or6. The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 6 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 5 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 4 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 3 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 24 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 13 to 23 weeks (e.g., the duration of thetreatment is selected from 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23weeks) and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and the HCV polymerase inhibitor, said at least two DAAs canalso include one or more additional DAAs selected from, for example, HCVprotease inhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 12 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 11 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 10 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and an HCV polymeraseinhibitor. The treatment lasts 9 weeks and does not includeadministration of any interferon or ribavirin (i.e., neither interferonnor ribavirin are administered). The DAAs can be administered at thesame or different dosing frequencies. The patient being treated can be atreatment naïve patient; a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder, or a null responder; or a patient unable totake interferon. The patient may be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6. Thetreatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and the HCVpolymerase inhibitor, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-7977, PSI-938,TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335,BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In another aspect, the present invention features a method of treatingHCV infection, comprising administering to a patient in need thereof aneffective amount of a combination of at least two DAAs, wherein said atleast two DAAs comprise Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (or a pharmaceutically acceptable saltthereof) and sofosbuvir. The treatment lasts 8 weeks and does notinclude administration of any interferon or ribavirin (i.e., neitherinterferon nor ribavirin are administered). The DAAs can be administeredat the same or different dosing frequencies. The patient being treatedcan be a treatment naïve patient; a treatment experienced patient,including, but not limited to, a relapser, an interferon partialresponder, an interferon non-responder, or a null responder; or apatient unable to take interferon. The patient may be infected with, forexample and without limitation, HCV genotype 1, such as HCV genotype 1aor HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6.The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and sofosbuvir, saidat least two DAAs can also include one or more additional DAAs selectedfrom, for example, HCV protease inhibitors, HCV polymerase inhibitors,or HCV NS5A inhibitors. Non-limiting examples of such additional DAAsinclude PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In another aspect, the present invention features a method of treatingHCV infection, comprising administering to a patient in need thereof aneffective amount of a combination of at least two DAAs, wherein said atleast two DAAs comprise Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (or a pharmaceutically acceptable saltthereof) and sofosbuvir. The treatment lasts 7 weeks and does notinclude administration of any interferon or ribavirin (i.e., neitherinterferon nor ribavirin are administered). The DAAs can be administeredat the same or different dosing frequencies. The patient being treatedcan be a treatment naïve patient; a treatment experienced patient,including, but not limited to, a relapser, an interferon partialresponder, an interferon non-responder, or a null responder; or apatient unable to take interferon. The patient may be infected with, forexample and without limitation, HCV genotype 1, such as HCV genotype 1aor HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6.The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and sofosbuvir, saidat least two DAAs can also include one or more additional DAAs selectedfrom, for example, HCV protease inhibitors, HCV polymerase inhibitors,or HCV NS5A inhibitors. Non-limiting examples of such additional DAAsinclude PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 6 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 5 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 4 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 3 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 24 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 13 to 23 weeks (e.g., the duration of the treatment is selectedfrom 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 weeks) and does notinclude administration of any interferon or ribavirin (i.e., neitherinterferon nor ribavirin are administered). The DAAs can be administeredat the same or different dosing frequencies. The patient being treatedcan be a treatment naïve patient; a treatment experienced patient,including, but not limited to, a relapser, an interferon partialresponder, an interferon non-responder, or a null responder; or apatient unable to take interferon. The patient may be infected with, forexample and without limitation, HCV genotype 1, such as HCV genotype 1aor HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6.The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 1(or a salt thereof), Compound 2 (or a salt thereof) and sofosbuvir, saidat least two DAAs can also include one or more additional DAAs selectedfrom, for example, HCV protease inhibitors, HCV polymerase inhibitors,or HCV NS5A inhibitors. Non-limiting examples of such additional DAAsinclude PSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190,GS-9451, BI-201335, BI-207127, telaprevir, VX-222, mericitabine, anddanoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 12 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 11 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 10 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 1 (or apharmaceutically acceptable salt thereof), Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 9 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir, said at least two DAAs can also include one ormore additional DAAs selected from, for example, HCV proteaseinhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In another aspect, the present invention features a method of treatingHCV infection, comprising administering to a patient in need thereof aneffective amount of a combination of at least two DAAs, wherein said atleast two DAAs comprise Compound 2 (or a pharmaceutically acceptablesalt thereof) and sofosbuvir. The treatment lasts 8 weeks and does notinclude administration of any interferon or ribavirin (i.e., neitherinterferon nor ribavirin are administered). The DAAs can be administeredat the same or different dosing frequencies. The patient being treatedcan be a treatment naïve patient; a treatment experienced patient,including, but not limited to, a relapser, an interferon partialresponder, an interferon non-responder, or a null responder; or apatient unable to take interferon. The patient may be infected with, forexample and without limitation, HCV genotype 1, such as HCV genotype 1aor HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6.The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 2(or a salt thereof) and sofosbuvir, said at least two DAAs can alsoinclude one or more additional DAAs selected from, for example, HCVprotease inhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In another aspect, the present invention features a method of treatingHCV infection, comprising administering to a patient in need thereof aneffective amount of a combination of at least two DAAs, wherein said atleast two DAAs comprise Compound 2 (or a pharmaceutically acceptablesalt thereof) and sofosbuvir. The treatment lasts 7 weeks and does notinclude administration of any interferon or ribavirin (i.e., neitherinterferon nor ribavirin are administered). The DAAs can be administeredat the same or different dosing frequencies. The patient being treatedcan be a treatment naïve patient; a treatment experienced patient,including, but not limited to, a relapser, an interferon partialresponder, an interferon non-responder, or a null responder; or apatient unable to take interferon. The patient may be infected with, forexample and without limitation, HCV genotype 1, such as HCV genotype 1aor HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6.The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 2(or a salt thereof) and sofosbuvir, said at least two DAAs can alsoinclude one or more additional DAAs selected from, for example, HCVprotease inhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 6 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 5 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 4 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 3 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 24 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 13 to 23 weeks (e.g., the duration of the treatment is selectedfrom 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 weeks) and does notinclude administration of any interferon or ribavirin (i.e., neitherinterferon nor ribavirin are administered). The DAAs can be administeredat the same or different dosing frequencies. The patient being treatedcan be a treatment naïve patient; a treatment experienced patient,including, but not limited to, a relapser, an interferon partialresponder, an interferon non-responder, or a null responder; or apatient unable to take interferon. The patient may be infected with, forexample and without limitation, HCV genotype 1, such as HCV genotype 1aor HCV genotype 1b; or HCV genotype 2 or 3; or HCV genotype 4, 5 or 6.The treatment according to this aspect of the technology may also beeffective against other HCV genotypes. The DAAs can be administeredaround the same time or at different times. In addition to Compound 2(or a salt thereof) and sofosbuvir, said at least two DAAs can alsoinclude one or more additional DAAs selected from, for example, HCVprotease inhibitors, HCV polymerase inhibitors, or HCV NS5A inhibitors.Non-limiting examples of such additional DAAs include PSI-938, TMC-435,BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451, BI-201335, BI-207127,telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 12 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 11 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 10 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In yet another aspect, the present invention features a method oftreating HCV infection, comprising administering to a patient in needthereof an effective amount of a combination of at least two DAAs,wherein said at least two DAAs comprise Compound 2 (or apharmaceutically acceptable salt thereof) and sofosbuvir. The treatmentlasts 9 weeks and does not include administration of any interferon orribavirin (i.e., neither interferon nor ribavirin are administered). TheDAAs can be administered at the same or different dosing frequencies.The patient being treated can be a treatment naïve patient; a treatmentexperienced patient, including, but not limited to, a relapser, aninterferon partial responder, an interferon non-responder, or a nullresponder; or a patient unable to take interferon. The patient may beinfected with, for example and without limitation, HCV genotype 1, suchas HCV genotype 1a or HCV genotype 1b; or HCV genotype 2 or 3; or HCVgenotype 4, 5 or 6. The treatment according to this aspect of thetechnology may also be effective against other HCV genotypes. The DAAscan be administered around the same time or at different times. Inaddition to Compound 2 (or a salt thereof) and sofosbuvir, said at leasttwo DAAs can also include one or more additional DAAs selected from, forexample, HCV protease inhibitors, HCV polymerase inhibitors, or HCV NS5Ainhibitors. Non-limiting examples of such additional DAAs includePSI-938, TMC-435, BMS-790052, BMS-650032, GS-5885, GS-9190, GS-9451,BI-201335, BI-207127, telaprevir, VX-222, mericitabine, and danoprevir.

In each aspect, embodiment, example or method described herein, Compound1 (or a pharmaceutically acceptable salt thereof) can be administered,for example and without limitation, from 100 mg to 600 mg once daily,and Compound 2 (or a pharmaceutically acceptable salt thereof) can beadministered, for example and without limitation, from 50 to 500 mg oncedaily. More preferably, Compound 1 (or a pharmaceutically acceptablesalt thereof) is administered from 200 mg to 600 mg once daily, andCompound 2 (or a pharmaceutically acceptable salt thereof) isadministered from 100 to 500 mg once daily. Highly preferably, Compound1 (or a pharmaceutically acceptable salt thereof) is administered from400 mg to 600 mg once daily, and Compound 2 (or a pharmaceuticallyacceptable salt thereof) is administered from 100 to 500 mg once daily.Most preferably, Compound 1 (or a pharmaceutically acceptable saltthereof) is administered from 200 mg to 300 mg once daily, and Compound2 (or a pharmaceutically acceptable salt thereof) is administered from100 to 500 mg once daily. Preferably, Compound 1 (or a pharmaceuticallyacceptable salt thereof) can be administered 200 mg once daily, andCompound 2 (or a pharmaceutically acceptable salt thereof) isadministered 120 mg once daily. Also preferably, Compound 1 (or apharmaceutically acceptable salt thereof) can be administered 300 mgonce daily, and Compound 2 (or a pharmaceutically acceptable saltthereof) is administered 120 mg once daily. For another example,Compound 1 (or a pharmaceutically acceptable salt thereof) can beadministered 400 mg once daily, and Compound 2 (or a pharmaceuticallyacceptable salt thereof) is administered 120 mg once daily. For yetanother example, Compound 1 (or a pharmaceutically acceptable saltthereof) can be administered 400 mg once daily, and Compound 2 (or apharmaceutically acceptable salt thereof) can be administered 240 mgonce daily.

In each aspect, embodiment, example or method described herein,sofosbuvir can be administered, for example and without limitation, 400mg once daily.

A method of the present invention can be used to treat a naïve patientor a treatment experienced patient. Treatment experienced patientsinclude interferon non-responders (e.g., null responders), partialresponders, and relapsers. A method of the present invention can also beused to treat patients who are not candidates for interferon treatment.Patients who are not candidates for interferon treatment include, butare not limited to, one or more of the following groups: patientsintolerant to interferon, patients who refuse to take interferontreatment, patients with medical conditions which preclude them fromtaking interferon, and patients who have an increased risk of sideeffects or infection by taking interferon.

In any method described herein wherein Compound 1 and Compound 2 areused, one or more additional DAAs can be optionally used in thetreatment regimen in addition to Compound 1 (or a salt thereof) andCompound 2 (or a salt thereof). Similarly, in any method describedherein wherein Compound 1, Compound 2 and sofosbuvir are used, one ormore additional DAAs can be optionally used in the treatment regimen inaddition to Compound 1 (or a salt thereof), Compound 2 (or a saltthereof) and sofosbuvir. Likewise, in any method described hereinwherein Compound 2 and sofosbuvir are used, one or more additional DAAscan be optionally used in the treatment regimen in addition to Compound2 (or a salt thereof) and sofosbuvir. These additional DAAs can be HCVprotease inhibitors, HCV nucleoside or nucleotide polymerase inhibitors,HCV non-nucleoside polymerase inhibitors, HCV NS3B inhibitors, HCV NS4Ainhibitors, HCV NS5A inhibitors, HCV NS5B inhibitors, HCV entryinhibitors, cyclophilin inhibitors, or combinations thereof.

Preferred HCV protease inhibitors for this purpose include, but are notlimited to, telaprevir (Vertex), boceprevir (Merck), BI-201335(Boehringer Ingelheim), GS-9451 (Gilead), and BMS-650032 (BMS). Othersuitable protease inhibitors include, but are not limited to, ACH-1095(Achillion), ACH-1625 (Achillion), ACH-2684 (Achillion), AVL-181(Avila), AVL-192 (Avila), BMS-650032 (BMS), danoprevir (RG7227/ITMN-191,Roche), GS-9132 (Gilead), GS-9256 (Gilead), IDX-136 (Idenix), IDX-316(Idenix), IDX-320 (Idenix), MK-5172 (Merck), narlaprevir(Schering-Plough Corp), PHX-1766 (Phenomix), TMC-435 (Tibotec),vaniprevir (MK-7009, Merck), VBY708 (Virobay), VX-500 (Vertex), VX-813(Vertex), VX-985 (Vertex), or a combination thereof.

Preferred non-nucleoside HCV polymerase inhibitors for use in thepresent invention include, but are not limited to, GS-9190 (Gilead),BI-207127 (Boehringer Ingelheim), and VX-222 (VCH-222) (Vertex &ViraChem). Preferred nucleotide HCV polymerase inhibitors include, butare not limited to, PSI-7977 (Gilead), and PSI-938 (Gilead). Othersuitable and non-limiting examples of suitable HCV polymerase inhibitorsinclude ANA-598 (Anadys), BI-207127 (Boehringer Ingelheim), BILB-1941(Boehringer Ingelheim), BMS-791325 (BMS), filibuvir, GL59728 (Glaxo),GL60667 (Glaxo), GS-9669 (Gilead), IDX-375 (Idenix), MK-3281 (Merck),tegobuvir, TMC-647055 (Tibotec), VCH-759 (Vertex & ViraChem), VCH-916(ViraChem), VX-759 (Vertex), GS-6620 (Gilead), IDX-102 (Idenix), IDX-184(Idenix), INX-189 (Inhibitex), MK-0608 (Merck), RG7128 (Roche), TMC64912(Medivir), GSK625433 (GlaxoSmithKline), BCX-4678 (BioCryst), ALS-2200(Alios BioPharma/Vertex), ALS-2158 (Alios BioPharma/Vertex), or acombination thereof. A polymerase inhibitor may be a nucleoside ornucleotide polymerase inhibitor, such as GS-6620 (Gilead), IDX-102(Idenix), IDX-184 (Idenix), INX-189 (Inhibitex), MK-0608 (Merck),PSI-7977 (Gilead), PSI-938 (Gilead), RG7128 (Roche), TMC64912 (Medivir),ALS-2200 (Alios BioPharma/Vertex), ALS-2158 (Alios BioPharma/Vertex), ora combination therefore. A polymerase inhibitor may also be anon-nucleoside polymerase inhibitor, such as PF-00868554 (Pfizer),ANA-598 (Anadys), BI-207127 (Boehringer Ingelheim), BILB-1941(Boehringer Ingelheim), BMS-791325 (BMS), filibuvir, GL59728 (Glaxo),GL60667 (Glaxo), GS-9669 (Gilead), IDX-375 (Idenix), MK-3281 (Merck),tegobuvir (Gilead), TMC-647055 (Tibotec), VCH-759 (Vertex & ViraChem),VCH-916 (ViraChem), VX-222 (VCH-222) (Vertex & ViraChem), VX-759(Vertex), or a combination thereof.

Preferred NS5A inhibitors include, but are not limited to, BMS-790052(BMS) and GS-5885 (Gilead). Non-limiting examples of suitable NS5Ainhibitors include GSK62336805 (GlaxoSmithKline), ACH-2928 (Achillion),AZD2836 (Astra-Zeneca), AZD7295 (Astra-Zeneca), BMS-790052 (BMS),BMS-824393 (BMS), GS-5885 (Gilead), PPI-1301 (Presidio), PPI-461(Presidio) A-831 (Arrow Therapeutics), A-689 (Arrow Therapeutics) or acombination thereof.

Non-limiting examples of suitable cyclophilin inhibitors includealisporovir (Novartis & Debiopharm), NM-811 (Novartis), SCY-635(Scynexis), or a combination thereof.

Non-limiting examples of suitable HCV entry inhibitors include ITX-4520(iTherx), ITX-5061 (iTherx), or a combination thereof.

Specific examples of other DAA agents that are suitable for inclusion ina method of the present invention include, but are not limited to,AP-H005, A-831 (Arrow Therapeutics) (NS5A inhibitor), A-689 (ArrowTherapeutics) (NS5A inhibitor), INX08189 (Inhibitex) (polymeraseinhibitor), ITMN-191 (Intermune/Roche) (NS3/4A Protease inhibitor),VBY-376 (Protease Inhibitor) (Virobay), ACH-1625 (Achillion, Proteaseinhibitor), IDX136 (Idenix, Protease Inhibitor), IDX316 (Idenix,Protease inhibitor), VX-813 (Vertex), SCH 900518 (Schering-Plough),TMC-435 (Tibotec), ITMN-191 (Intermune, Roche), MK-7009 (Merck), IDX-PI(Novartis), R7128 (Roche), PF-868554 (Pfizer) (non-nucleoside polymeraseinhibitor), PF-4878691 (Pfizer), IDX-184 (Idenix), IDX-375 (Idenix, NS5Bpolymerase inhibitor), PPI-461 (Presidio), BILB-1941 (BoehringerIngelheim), GS-9190 (Gilead), BMS-790052 (BMS), CTS-1027 (Conatus),GS-9620 (Gilead), PF-4878691 (Pfizer), R05303253 (Roche), ALS-2200(Alios BioPharma/Vertex), ALS-2158 (Alios BioPharma/Vertex), GSK62336805(GlaxoSmithKline), or any combinations thereof.

The chemical structures of some of these optional HCV inhibitors areprovided below:

Any HCV inhibitor or DAA described herein encompasses its suitable saltforms when it is used in therapeutic treatments or pharmaceuticalformulations.

In some embodiments, the present invention features methods for treatingpatients infected with HCV genotype 1, such as 1a or 1b. The methodscomprise administering to such a patient a combination of at least 2DAAs for no more than 12 weeks (e.g., the duration being 12, 11, 10, 9,8, 7, 6, 5, or 4 weeks), such as no more than 8 weeks (e.g., theduration being 8, 7, 6, 5, or 4 weeks), wherein the treatment does notinclude administration of either interferon or ribavirin, and said atleast 2 DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof) and Compound 2 (a pharmaceutically acceptable salt thereof).Compound 1 (or a pharmaceutically acceptable salt thereof) and Compound2 (a pharmaceutically acceptable salt thereof) can be administered intherapeutically effective amounts to provide a SVR (for example, atleast 75% SVR8, or preferably at least 80% SVR8, or highly preferably atleast 90% SVR8, or most preferably at least 95% SVR8) after thecompletion of the treatment. The patients may be treatment naïvepatients or treatment experienced patients. The treatment duration canbe no more than 12 weeks, including but not limited to, no more than 11weeks, no more than 10 weeks, no more than 9 weeks, but preferably nomore than 8 weeks, no more than 7 weeks, no more than 6 weeks, no morethan 5 weeks, no more than 4 weeks, or no more than 3 weeks, e.g., theduration being 12 weeks, or the duration being 11 weeks, or the durationbeing 10 weeks, or the duration being 9 weeks, or the duration being 8weeks, or the duration being 7 weeks, or the duration being 6 weeks, orthe duration being 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 or 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable salt thereof)and Compound 2 (a pharmaceutically acceptable salt thereof). Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (apharmaceutically acceptable salt thereof) can be administered intherapeutically effective amounts to provide a SVR (for example, atleast 75% SVR8, or preferably at least 80% SVR8, or highly preferably atleast 90% SVR8, or most preferably at least 95% SVR8) after thecompletion of the treatment. The patients may be treatment naïvepatients or treatment experienced patients. The treatment duration canbe no more than 12 weeks, including but not limited to, no more than 11weeks, no more than 10 weeks, no more than 9 weeks, but preferably nomore than 8 weeks, no more than 7 weeks, no more than 6 weeks, no morethan 5 weeks, no more than 4 weeks, or no more than 3 weeks, e.g., theduration being 12 weeks, or the duration being 11 weeks, or the durationbeing 10 weeks, or the duration being 9 weeks, or the duration being 8weeks, or the duration being 7 weeks, or the duration being 6 weeks, orthe duration being 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable salt thereof)and Compound 2 (a pharmaceutically acceptable salt thereof). Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (apharmaceutically acceptable salt thereof) can be administered intherapeutically effective amounts to provide a SVR (for example, atleast 75% SVR8, or preferably at least 80% SVR8, or highly preferably atleast 90% SVR8, or most preferably at least 95% SVR8) after thecompletion of the treatment. The patients may be treatment naïvepatients or treatment experienced patients. The treatment duration canbe no more than 12 weeks, including but not limited to, no more than 11weeks, no more than 10 weeks, no more than 9 weeks, but preferably nomore than 8 weeks, no more than 7 weeks, no more than 6 weeks, no morethan 5 weeks, no more than 4 weeks, or no more than 3 weeks, e.g., theduration being 12 weeks, or the duration being 11 weeks, or the durationbeing 10 weeks, or the duration being 9 weeks, or the duration being 8weeks, or the duration being 7 weeks, or the duration being 6 weeks, orthe duration being 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable salt thereof)and Compound 2 (a pharmaceutically acceptable salt thereof). Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (apharmaceutically acceptable salt thereof) can be administered intherapeutically effective amounts to provide a SVR (for example, atleast 75% SVR8, or preferably at least 80% SVR8, or highly preferably atleast 90% SVR8, or most preferably at least 95% SVR8) after thecompletion of the treatment. The patients may be treatment naïvepatients or treatment experienced patients. The treatment duration canbe no more than 12 weeks, including but not limited to, no more than 11weeks, no more than 10 weeks, no more than 9 weeks, but preferably nomore than 8 weeks, no more than 7 weeks, no more than 6 weeks, no morethan 5 weeks, no more than 4 weeks, or no more than 3 weeks, e.g., theduration being 12 weeks, or the duration being 11 weeks, or the durationbeing 10 weeks, or the duration being 9 weeks, or the duration being 8weeks, or the duration being 7 weeks, or the duration being 6 weeks, orthe duration being 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 4 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable salt thereof)and Compound 2 (a pharmaceutically acceptable salt thereof). Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (apharmaceutically acceptable salt thereof) can be administered intherapeutically effective amounts to provide a SVR (for example, atleast 75% SVR8, or preferably at least 80% SVR8, or highly preferably atleast 90% SVR8, or most preferably at least 95% SVR8) after thecompletion of the treatment. The patients may be treatment naïvepatients or treatment experienced patients. The treatment duration canbe no more than 12 weeks, including but not limited to, no more than 11weeks, no more than 10 weeks, no more than 9 weeks, but preferably nomore than 8 weeks, no more than 7 weeks, no more than 6 weeks, no morethan 5 weeks, no more than 4 weeks, or no more than 3 weeks, e.g., theduration being 12 weeks, or the duration being 11 weeks, or the durationbeing 10 weeks, or the duration being 9 weeks, or the duration being 8weeks, or the duration being 7 weeks, or the duration being 6 weeks, orthe duration being 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 5 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable salt thereof)and Compound 2 (a pharmaceutically acceptable salt thereof). Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (apharmaceutically acceptable salt thereof) can be administered intherapeutically effective amounts to provide a SVR (for example, atleast 75% SVR8, or preferably at least 80% SVR8, or highly preferably atleast 90% SVR8, or most preferably at least 95% SVR8) after thecompletion of the treatment. The patients may be treatment naïvepatients or treatment experienced patients. The treatment duration canbe no more than 12 weeks, including but not limited to, no more than 11weeks, no more than 10 weeks, no more than 9 weeks, but preferably nomore than 8 weeks, no more than 7 weeks, no more than 6 weeks, no morethan 5 weeks, no more than 4 weeks, or no more than 3 weeks, e.g., theduration being 12 weeks, or the duration being 11 weeks, or the durationbeing 10 weeks, or the duration being 9 weeks, or the duration being 8weeks, or the duration being 7 weeks, or the duration being 6 weeks, orthe duration being 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 6 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable salt thereof)and Compound 2 (a pharmaceutically acceptable salt thereof). Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (apharmaceutically acceptable salt thereof) can be administered intherapeutically effective amounts to provide a SVR (for example, atleast 75% SVR8, or preferably at least 80% SVR8, or highly preferably atleast 90% SVR8, or most preferably at least 95% SVR8) after thecompletion of the treatment. The patients may be treatment naïvepatients or treatment experienced patients. The treatment duration canbe no more than 12 weeks, including but not limited to, no more than 11weeks, no more than 10 weeks, no more than 9 weeks, but preferably nomore than 8 weeks, no more than 7 weeks, no more than 6 weeks, no morethan 5 weeks, no more than 4 weeks, or no more than 3 weeks, e.g., theduration being 12 weeks, or the duration being 11 weeks, or the durationbeing 10 weeks, or the duration being 9 weeks, or the duration being 8weeks, or the duration being 7 weeks, or the duration being 6 weeks, orthe duration being 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients infected with HCV genotype 1, such as 1a or 1b. The methodscomprise administering to such a patient a combination of at least 2DAAs for no more than 12 weeks (e.g., the duration being 12, 11, 10, 9,8, 7, 6, 5, or 4 weeks), such as no more than 8 weeks (e.g., theduration being 8, 7, 6, 5, or 4 weeks), wherein the treatment does notinclude administration of either interferon or ribavirin (i.e., neitherinterferon nor ribavirin are administered), and said at least 2 DAAscomprise Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and an HCVpolymerase inhibitor. Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andthe HCV polymerase inhibitor can be administered in therapeuticallyeffective amounts to provide a SVR (for example, at least 75% SVR8, orpreferably at least 80% SVR8, or highly preferably at least 90% SVR8, ormost preferably at least 95% SVR8) after the completion of thetreatment. The patients may be treatment naïve patients or treatmentexperienced patients. The treatment duration can be no more than 12weeks, including but not limited to, no more than 11 weeks, no more than10 weeks, no more than 9 weeks, but preferably no more than 8 weeks, nomore than 7 weeks, no more than 6 weeks, no more than 5 weeks, no morethan 4 weeks, or no more than 3 weeks, e.g., the duration being 12weeks, or the duration being 11 weeks, or the duration being 10 weeks,or the duration being 9 weeks, or the duration being 8 weeks, or theduration being 7 weeks, or the duration being 6 weeks, or the durationbeing 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 or 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) and anHCV polymerase inhibitor. Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (a pharmaceutically acceptable salt thereof)and the HCV polymerase inhibitor can be administered in therapeuticallyeffective amounts to provide a SVR (for example, at least 75% SVR8, orpreferably at least 80% SVR8, or highly preferably at least 90% SVR8, ormost preferably at least 95% SVR8) after the completion of thetreatment. The patients may be treatment naïve patients or treatmentexperienced patients. The treatment duration can be no more than 12weeks, including but not limited to, no more than 11 weeks, no more than10 weeks, no more than 9 weeks, but preferably no more than 8 weeks, nomore than 7 weeks, no more than 6 weeks, no more than 5 weeks, no morethan 4 weeks, or no more than 3 weeks, e.g., the duration being 12weeks, or the duration being 11 weeks, or the duration being 10 weeks,or the duration being 9 weeks, or the duration being 8 weeks, or theduration being 7 weeks, or the duration being 6 weeks, or the durationbeing 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) and anHCV polymerase inhibitor. Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (a pharmaceutically acceptable salt thereof)and the HCV polymerase inhibitor can be administered in therapeuticallyeffective amounts to provide a SVR (for example, at least 75% SVR8, orpreferably at least 80% SVR8, or highly preferably at least 90% SVR8, ormost preferably at least 95% SVR8) after the completion of thetreatment. The patients may be treatment naïve patients or treatmentexperienced patients. The treatment duration can be no more than 12weeks, including but not limited to, no more than 11 weeks, no more than10 weeks, no more than 9 weeks, but preferably no more than 8 weeks, nomore than 7 weeks, no more than 6 weeks, no more than 5 weeks, no morethan 4 weeks, or no more than 3 weeks, e.g., the duration being 12weeks, or the duration being 11 weeks, or the duration being 10 weeks,or the duration being 9 weeks, or the duration being 8 weeks, or theduration being 7 weeks, or the duration being 6 weeks, or the durationbeing 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) and anHCV polymerase inhibitor. Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (a pharmaceutically acceptable salt thereof)and the HCV polymerase inhibitor can be administered in therapeuticallyeffective amounts to provide a SVR (for example, at least 75% SVR8, orpreferably at least 80% SVR8, or highly preferably at least 90% SVR8, ormost preferably at least 95% SVR8) after the completion of thetreatment. The patients may be treatment naïve patients or treatmentexperienced patients. The treatment duration can be no more than 12weeks, including but not limited to, no more than 11 weeks, no more than10 weeks, no more than 9 weeks, but preferably no more than 8 weeks, nomore than 7 weeks, no more than 6 weeks, no more than 5 weeks, no morethan 4 weeks, or no more than 3 weeks, e.g., the duration being 12weeks, or the duration being 11 weeks, or the duration being 10 weeks,or the duration being 9 weeks, or the duration being 8 weeks, or theduration being 7 weeks, or the duration being 6 weeks, or the durationbeing 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 4 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) and anHCV polymerase inhibitor. Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (a pharmaceutically acceptable salt thereof)and the HCV polymerase inhibitor can be administered in therapeuticallyeffective amounts to provide a SVR (for example, at least 75% SVR8, orpreferably at least 80% SVR8, or highly preferably at least 90% SVR8, ormost preferably at least 95% SVR8) after the completion of thetreatment. The patients may be treatment naïve patients or treatmentexperienced patients. The treatment duration can be no more than 12weeks, including but not limited to, no more than 11 weeks, no more than10 weeks, no more than 9 weeks, but preferably no more than 8 weeks, nomore than 7 weeks, no more than 6 weeks, no more than 5 weeks, no morethan 4 weeks, or no more than 3 weeks, e.g., the duration being 12weeks, or the duration being 11 weeks, or the duration being 10 weeks,or the duration being 9 weeks, or the duration being 8 weeks, or theduration being 7 weeks, or the duration being 6 weeks, or the durationbeing 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 5 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) and anHCV polymerase inhibitor. Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (a pharmaceutically acceptable salt thereof)and the HCV polymerase inhibitor can be administered in therapeuticallyeffective amounts to provide a SVR (for example, at least 75% SVR8, orpreferably at least 80% SVR8, or highly preferably at least 90% SVR8, ormost preferably at least 95% SVR8) after the completion of thetreatment. The patients may be treatment naïve patients or treatmentexperienced patients. The treatment duration can be no more than 12weeks, including but not limited to, no more than 11 weeks, no more than10 weeks, no more than 9 weeks, but preferably no more than 8 weeks, nomore than 7 weeks, no more than 6 weeks, no more than 5 weeks, no morethan 4 weeks, or no more than 3 weeks, e.g., the duration being 12weeks, or the duration being 11 weeks, or the duration being 10 weeks,or the duration being 9 weeks, or the duration being 8 weeks, or theduration being 7 weeks, or the duration being 6 weeks, or the durationbeing 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 6 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) and anHCV polymerase inhibitor. Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (a pharmaceutically acceptable salt thereof)and the HCV polymerase inhibitor can be administered in therapeuticallyeffective amounts to provide a SVR (for example, at least 75% SVR8, orpreferably at least 80% SVR8, or highly preferably at least 90% SVR8, ormost preferably at least 95% SVR8) after the completion of thetreatment. The patients may be treatment naïve patients or treatmentexperienced patients. The treatment duration can be no more than 12weeks, including but not limited to, no more than 11 weeks, no more than10 weeks, no more than 9 weeks, but preferably no more than 8 weeks, nomore than 7 weeks, no more than 6 weeks, no more than 5 weeks, no morethan 4 weeks, or no more than 3 weeks, e.g., the duration being 12weeks, or the duration being 11 weeks, or the duration being 10 weeks,or the duration being 9 weeks, or the duration being 8 weeks, or theduration being 7 weeks, or the duration being 6 weeks, or the durationbeing 5 weeks, or the duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients infected with HCV genotype 1, such as 1a or 1b. The methodscomprise administering to such a patient a combination of at least 2DAAs for no more than 12 weeks (e.g., the duration being 12, 11, 10, 9,8, 7, 6, 5, or 4 weeks), such as no more than 8 weeks (e.g., theduration being 8, 7, 6, 5, or 4 weeks), wherein the treatment does notinclude administration of either interferon or ribavirin, and said atleast 2 DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir. Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and sofosbuvircan be administered in therapeutically effective amounts to provide aSVR (for example, at least 75% SVR8, or preferably at least 80% SVR8, orhighly preferably at least 90% SVR8, or most preferably at least 95%SVR8) after the completion of the treatment. The patients may betreatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 or 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir. Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and sofosbuvircan be administered in therapeutically effective amounts to provide aSVR (for example, at least 75% SVR8, or preferably at least 80% SVR8, orhighly preferably at least 90% SVR8, or most preferably at least 95%SVR8) after the completion of the treatment. The patients may betreatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir. Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and sofosbuvircan be administered in therapeutically effective amounts to provide aSVR (for example, at least 75% SVR8, or preferably at least 80% SVR8, orhighly preferably at least 90% SVR8, or most preferably at least 95%SVR8) after the completion of the treatment. The patients may betreatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir. Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and sofosbuvircan be administered in therapeutically effective amounts to provide aSVR (for example, at least 75% SVR8, or preferably at least 80% SVR8, orhighly preferably at least 90% SVR8, or most preferably at least 95%SVR8) after the completion of the treatment. The patients may betreatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 4 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir. Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and sofosbuvircan be administered in therapeutically effective amounts to provide aSVR (for example, at least 75% SVR8, or preferably at least 80% SVR8, orhighly preferably at least 90% SVR8, or most preferably at least 95%SVR8) after the completion of the treatment. The patients may betreatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 5 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir. Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and sofosbuvircan be administered in therapeutically effective amounts to provide aSVR (for example, at least 75% SVR8, or preferably at least 80% SVR8, orhighly preferably at least 90% SVR8, or most preferably at least 95%SVR8) after the completion of the treatment. The patients may betreatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 6 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir. Compound 1 (or a pharmaceutically acceptable salt thereof),Compound 2 (a pharmaceutically acceptable salt thereof) and sofosbuvircan be administered in therapeutically effective amounts to provide aSVR (for example, at least 75% SVR8, or preferably at least 80% SVR8, orhighly preferably at least 90% SVR8, or most preferably at least 95%SVR8) after the completion of the treatment. The patients may betreatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients infected with HCV genotype 1, such as 1a or 1b. The methodscomprise administering to such a patient a combination of at least 2DAAs for no more than 12 weeks (e.g., the duration being 12, 11, 10, 9,8, 7, 6, 5, or 4 weeks), such as no more than 8 weeks (e.g., theduration being 8, 7, 6, 5, or 4 weeks), wherein the treatment does notinclude administration of either interferon or ribavirin, and said atleast 2 DAAs comprise Compound 2 (a pharmaceutically acceptable saltthereof) and sofosbuvir. Compound 2 (a pharmaceutically acceptable saltthereof) and sofosbuvir can be administered in therapeutically effectiveamounts to provide a SVR (for example, at least 75% SVR8, or preferablyat least 80% SVR8, or highly preferably at least 90% SVR8, or mostpreferably at least 95% SVR8) after the completion of the treatment. Thepatients may be treatment naïve patients or treatment experiencedpatients. The treatment duration can be no more than 12 weeks, includingbut not limited to, no more than 11 weeks, no more than 10 weeks, nomore than 9 weeks, but preferably no more than 8 weeks, no more than 7weeks, no more than 6 weeks, no more than 5 weeks, no more than 4 weeks,or no more than 3 weeks, e.g., the duration being 12 weeks, or theduration being 11 weeks, or the duration being 10 weeks, or the durationbeing 9 weeks, or the duration being 8 weeks, or the duration being 7weeks, or the duration being 6 weeks, or the duration being 5 weeks, orthe duration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 or 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir. Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir can be administered in therapeutically effective amountsto provide a SVR (for example, at least 75% SVR8, or preferably at least80% SVR8, or highly preferably at least 90% SVR8, or most preferably atleast 95% SVR8) after the completion of the treatment. The patients maybe treatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 2 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir. Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir can be administered in therapeutically effective amountsto provide a SVR (for example, at least 75% SVR8, or preferably at least80% SVR8, or highly preferably at least 90% SVR8, or most preferably atleast 95% SVR8) after the completion of the treatment. The patients maybe treatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 3 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir. Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir can be administered in therapeutically effective amountsto provide a SVR (for example, at least 75% SVR8, or preferably at least80% SVR8, or highly preferably at least 90% SVR8, or most preferably atleast 95% SVR8) after the completion of the treatment. The patients maybe treatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 4 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir. Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir can be administered in therapeutically effective amountsto provide a SVR (for example, at least 75% SVR8, or preferably at least80% SVR8, or highly preferably at least 90% SVR8, or most preferably atleast 95% SVR8) after the completion of the treatment. The patients maybe treatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 5 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir. Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir can be administered in therapeutically effective amountsto provide a SVR (for example, at least 75% SVR8, or preferably at least80% SVR8, or highly preferably at least 90% SVR8, or most preferably atleast 95% SVR8) after the completion of the treatment. The patients maybe treatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

In some embodiments, the present invention features methods for treatingpatients with HCV genotype 6 infection. The methods compriseadministering to such a patient a combination of at least 2 DAAs for nomore than 12 weeks (e.g., the duration being 12, 11, 10, 9, 8, 7, 6, 5,or 4 weeks), such as no more than 8 weeks (e.g., the duration being 8,7, 6, 5, or 4 weeks), wherein the treatment does not includeadministration of either interferon or ribavirin, and said at least 2DAAs comprise Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir. Compound 2 (a pharmaceutically acceptable salt thereof)and sofosbuvir can be administered in therapeutically effective amountsto provide a SVR (for example, at least 75% SVR8, or preferably at least80% SVR8, or highly preferably at least 90% SVR8, or most preferably atleast 95% SVR8) after the completion of the treatment. The patients maybe treatment naïve patients or treatment experienced patients. Thetreatment duration can be no more than 12 weeks, including but notlimited to, no more than 11 weeks, no more than 10 weeks, no more than 9weeks, but preferably no more than 8 weeks, no more than 7 weeks, nomore than 6 weeks, no more than 5 weeks, no more than 4 weeks, or nomore than 3 weeks, e.g., the duration being 12 weeks, or the durationbeing 11 weeks, or the duration being 10 weeks, or the duration being 9weeks, or the duration being 8 weeks, or the duration being 7 weeks, orthe duration being 6 weeks, or the duration being 5 weeks, or theduration being 4 weeks.

It will be understood that the specific dose level for any particularpatient will depend upon a variety of factors including the activity ofthe specific compound employed, the age, body weight, general health,sex, diet, time of administration, route of administration, rate ofexcretion, drug combination, and the severity of the disease undergoingtherapy.

In any method described herein wherein Compound 1 and Compound 2 areused, Compound 1 (or a pharmaceutically acceptable salt thereof) andCompound 2 (a pharmaceutically acceptable salt thereof) may beco-formulated in a single dosage form. Non-limiting examples of suitabledosage forms include liquid or solid dosage forms. Preferably, Compound1 and Compound 2 are formulated in a single solid dosage form in whichat least one of the DAAs is in an amorphous form, or highly preferablymolecularly dispersed, in a matrix which comprises a pharmaceuticallyacceptable water-soluble polymer and a pharmaceutically acceptablesurfactant. The other DAAs can also be in an amorphous form ormolecularly dispersed in the matrix, or formulated in different form(s)(e.g., in a crystalline form). More preferably, each of the two DAAs isin an amorphous form, or highly preferably molecularly dispersed, in amatrix which comprises a pharmaceutically acceptable water-solublepolymer and a pharmaceutically acceptable surfactant.

In any method described herein wherein Compound 1, Compound 2 andsofosbuvir are used, Compound 1 (or a pharmaceutically acceptable saltthereof), Compound 2 (a pharmaceutically acceptable salt thereof) andsofosbuvir may be co-formulated in a single dosage form. Non-limitingexamples of suitable dosage forms include liquid or solid dosage forms.Preferably, Compound 1, Compound 2 and sofosbuvir are formulated in asingle solid dosage form in which at least one of the DAAs is in anamorphous form, or highly preferably molecularly dispersed, in a matrixwhich comprises a pharmaceutically acceptable water-soluble polymer anda pharmaceutically acceptable surfactant. The other DAAs can also be inan amorphous form or molecularly dispersed in the matrix, or formulatedin different form(s) (e.g., in a crystalline form).

In any method described herein wherein Compound 2 and sofosbuvir areused, Compound 2 (or a pharmaceutically acceptable salt thereof) andsofosbuvir may be co-formulated in a single dosage form. Non-limitingexamples of suitable dosage forms include liquid or solid dosage forms.Preferably, Compound 2 and sofosbuvir are formulated in a single soliddosage form in which at least one of the DAAs is in an amorphous form,or highly preferably molecularly dispersed, in a matrix which comprisesa pharmaceutically acceptable water-soluble polymer and apharmaceutically acceptable surfactant. The other DAAs can also be in anamorphous form or molecularly dispersed in the matrix, or formulated indifferent form(s) (e.g., in a crystalline form).

In any method described herein, the patient being treated can be atreatment-naïve patient.

In any method described herein, the patient being treated can be aninterferon non-responder.

In any method described herein, the patient being treated can be aninterferon null-responder.

In any method described herein, the patient being treated can be withoutcirrhosis.

In any method described herein, the patient being treated can be acirrhotic patient.

In any method described herein, the patient being treated can be apatient with compensated cirrhosis.

In any method described herein where Compound 1 and Compound 2 are used,the DAAs employed in the method can consist of Compound 1 and Compound2. In any method described herein where Compound 1 and Compound 2 areused, the DAAs employed in the method can consist of Compound 1 andCompound 2. In any method described herein where Compound 1 and Compound2 are used, the DAAs employed in the method can consist of Compound 1(or a pharmaceutically acceptable salt thereof) and Compound 2 (or apharmaceutically acceptable salt thereof). In any method describedherein where Compound 1 and Compound 2 are used, the DAAs employed inthe method can consist of Compound 1 (or a pharmaceutically acceptablesalt thereof), Compound 2 (or a pharmaceutically acceptable saltthereof) and a HCV nucleotide polymerase inhibitor. In any methoddescribed herein where Compound 1 and Compound 2 are used, the DAAsemployed in the method can consist of Compound 1, Compound 2 and a HCVnucleotide polymerase inhibitor. In any method described herein whereCompound 1 and Compound 2 are used, the DAAs employed in the method canconsist of Compound 1 and Compound 2. In any method described hereinwhere Compound 1 and Compound 2 are used, Compound 1 and Compound 2 canbe administered with food. In any method described herein where Compound1 and Compound 2 are used, Compound 1 and Compound 2 can be administeredwithout food.

In any method described herein, the patient can have renal impairment,include hemodialysis. In any method described herein, the patient canhave chronic kidney disease (CKD) stage 3b (eGFR 30 to <45 mL/min/1.73m²), stage 4 (eGFR 15 to <30 mL/min/1.73 m²) or stage 5 (eGFR <15mL/min/1.73 m² or dialysis-dependent). In any method described herein,the patient can have HIV co-infection.

It is also contemplated a method of treating HCV, said method comprisingadministering to a patient in need thereof an effective amount of acombination of two or more DAAs. The treatment lasts 4 weeks and doesnot include administration of any interferon or ribavirin (i.e.,interferon- and ribavirin-free). The DAAs can be administered at thesame or different dosing frequency. The patient being treated can be atreatment naïve patient, a treatment experienced patient, including, butnot limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 is(2R,6S,13aS,14aR,16aS,Z)—N-(cyclopropylsulfonyl)-6-(5-methylpyrazine-2-carboxamido)-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxamide,and Compound 4 is as dimethyl (2S,2'S)-1,1′-((2S,2'S)-2,2′-(4,4′-((2S,5S)-1-(4-tert-butylphenyl)pyrrolidine-2,5,diyl)bis(4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl)bis(3-methyl-1-oxobutane-2, 1-diyl)dicarbamate, both of which aredescribed in U.S. Patent Application Publication No. 2013/0102526, filedOct. 19, 2012 and entitled “Methods for Treating HCV”, which isincorporated herein by reference in its entirety. Compound 3 preferablyis co-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. It is believed that the combination ofCompound 3, Compound 4, and sofosbuvir, without ribavirin andinterferon, can achieve at least about 80% SVR rate against HCV genotype1 after 4-week treatment. In another example, the combination of two ormore DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 5 weeksand does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. It is believed that the combination ofCompound 3, Compound 4, and sofosbuvir, without ribavirin andinterferon, can achieve at least about 80% SVR rate against HCV genotype1 after 5-week treatment. In another example, the combination of two ormore DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 6 weeksand does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. In another example, the combination of twoor more DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 7 weeksand does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. In another example, the combination of twoor more DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 8 weeksand does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. In another example, the combination of twoor more DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 9 weeksand does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. In another example, the combination of twoor more DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 10weeks and does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. In another example, the combination of twoor more DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 11weeks and does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. In another example, the combination of twoor more DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

It is further contemplated a method of treating HCV, said methodcomprising administering to a patient in need thereof an effectiveamount of a combination of two or more DAAs. The treatment lasts 12weeks and does not include administration of any interferon or ribavirin(i.e., interferon- and ribavirin-free). The DAAs can be administered atthe same or different dosing frequency. The patient being treated can bea treatment naïve patient, a treatment experienced patient, including,but not limited to, a relapser, an interferon partial responder, aninterferon non-responder (e.g., a null responder), or a patient unableto take interferon. The patient can be infected with, for example andwithout limitation, HCV genotype 1, such as HCV genotype 1a or HCVgenotype 1b; or HCV genotype 2 or 3. The treatment according to thisaspect can also be effective against other HCV genotypes. The DAAs canbe administered around the same time or at different times, and can beco-formulated in a single formulation or formulated in differentcompositions. Each DAA can be selected from HCV protease inhibitors, HCVpolymerase inhibitors, or HCV NS5A inhibitors. For instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV polymerase inhibitor (e.g., acombination of at least one HCV protease inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least oneHCV protease inhibitor and at least one nucleoside or nucleotidepolymerase inhibitor, or a combination of at least one HCV proteaseinhibitor, at least one nucleoside or nucleotide polymerase inhibitorand at least one non-nucleoside inhibitor). For another instance, thecombination of two or more DAAs can be a combination of at least one HCVprotease inhibitor and at least one HCV NS5A inhibitor. For stillanother instance, the combination of two or more DAAs can be acombination of at least one HCV protease inhibitor, at least one HCVpolymerase inhibitor, and at least one HCV NS5A inhibitor. For anotherinstance, the combination of two or more DAAs can be a combination of atleast two HCV polymerase inhibitors (e.g., a combination of at least twonucleoside or nucleotide polymerase inhibitors, or a combination of atleast one nucleoside or nucleotide polymerase inhibitor and at least onenon-nucleoside polymerase inhibitor, or a combination of at least twonon-nucleoside polymerase inhibitors). For another instance, thecombination of two or more DAAs can be a combination of at least two HCVprotease inhibitors. For another instance, the combination of two ormore DAAs can be a combination of at least two HCV NS5A inhibitors. Foranother instance, the combination of two or more DAAs can be acombination of at least one HCV polymerase inhibitor and at least oneNS5A inhibitor (e.g., a combination of at least one HCV NS5A inhibitorand at least one non-nucleoside polymerase inhibitor, or a combinationof at least one HCV NS5A inhibitor and at least one nucleoside ornucleotide polymerase inhibitor, or a combination of at least one HCVNS5A inhibitor, at least one nucleoside or nucleotide polymeraseinhibitor and at least one non-nucleoside polymerase inhibitor). In oneexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir. Compound 3 preferably isco-administered with ritonavir. More preferably, Compound 3 isco-formulated with ritonavir. In another example, the combination of twoor more DAAs is a combination of Compound 3, Compound 4, and sofosbuvir;and the patient is infected with HCV genotype 1. In another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the patient is a treatment-naïve patient infectedwith HCV genotype 1. In another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and thepatient is an interferon non-responder infected with HCV genotype 1. Inanother example, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor.In another example, the combination of two or more DAAs is a combinationof sofosbuvir, an HCV NS5A inhibitor, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In anotherexample, the combination of two or more DAAs is a combination ofsofosbuvir, an HCV NS5A inhibitor, and another HCV polymerase inhibitor;and the patient is a treatment-naïve patient infected with HCVgenotype 1. In another example, the combination of two or more DAAs is acombination of sofosbuvir, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, an HCV NS5A inhibitor, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is a treatment-naïve patient infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV NS5A inhibitor, and an HCV protease inhibitor; andthe patient is an interferon non-responder infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor. In yet another example, the combination of two or more DAAscomprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisessofosbuvir, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises sofosbuvir, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor. In another example, the combination oftwo or more DAAs is a combination of IDX21437, an HCV NS5A inhibitor,and another HCV polymerase inhibitor; and the patient is infected withHCV genotype 1. In another example, the combination of two or more DAAsis a combination of IDX21437, an HCV NS5A inhibitor, and another HCVpolymerase inhibitor; and the patient is a treatment-naïve patientinfected with HCV genotype 1. In another example, the combination of twoor more DAAs is a combination of IDX21437, an HCV NS5A inhibitor, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, an HCV NS5Ainhibitor, and an HCV protease inhibitor; and the patient is infectedwith HCV genotype 1. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV NS5A inhibitor, and an HCV proteaseinhibitor; and the patient is an interferon non-responder infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is infected with HCV genotype 1.In yet another example, the combination of two or more DAAs comprisesIDX21437, an HCV protease inhibitor, and another HCV polymeraseinhibitor; and the patient is a treatment-naïve patient infected withHCV genotype 1. In yet another example, the combination of two or moreDAAs comprises IDX21437, an HCV protease inhibitor, and another HCVpolymerase inhibitor; and the patient is an interferon non-responderinfected with HCV genotype 1. In yet another example, the combination oftwo or more DAAs comprises sofosbuvir, GS-5885, and another HCVpolymerase inhibitor. In yet another example, the combination of two ormore DAAs comprises sofosbuvir, GS-5885, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is a treatment-naïve patient infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and another HCV polymerase inhibitor; and thepatient is an interferon non-responder infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and another HCV polymerase inhibitor; and thepatient is infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, andanother HCV polymerase inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5885, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5885, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5885, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5885, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises sofosbuvir, GS-5816, and anHCV protease inhibitor. In yet another example, the combination of twoor more DAAs comprises sofosbuvir, GS-5816, and an HCV proteaseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprisessofosbuvir, GS-5816, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises sofosbuvir,GS-5816, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and anotherHCV polymerase inhibitor. In yet another example, the combination of twoor more DAAs comprises IDX21437, MK-8742, and another HCV polymeraseinhibitor; and the patient is infected with HCV genotype 1. In yetanother example, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and another HCV polymerase inhibitor; and the patient is aninterferon non-responder infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor. In yet another example, thecombination of two or more DAAs comprises IDX21437, MK-8742, and an HCVprotease inhibitor; and the patient is infected with HCV genotype 1. Inyet another example, the combination of two or more DAAs comprisesIDX21437, MK-8742, and an HCV protease inhibitor; and the patient is atreatment-naïve patient infected with HCV genotype 1. In yet anotherexample, the combination of two or more DAAs comprises IDX21437,MK-8742, and an HCV protease inhibitor; and the patient is an interferonnon-responder infected with HCV genotype 1. In still another example,the combination of two or more DAAs is a combination of Compound 3,Compound 4, and sofosbuvir; and the method comprises administering 100or 200 mg Compound 3 together with 100 mg ritonavir once daily, 25 mgcompound 4 once daily, and 400 mg sofosbuvir once daily. In stillanother example, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is infected with HCV genotype 1. In still anotherexample, the combination of two or more DAAs is a combination ofCompound 3, Compound 4, and sofosbuvir; and the method comprisesadministering 100 or 200 mg Compound 3 together with 100 mg ritonavironce daily, 25 mg compound 4 once daily, and 400 mg sofosbuvir oncedaily; and the patient is a treatment-naïve patient infected with HCVgenotype 1. In still another example, the combination of two or moreDAAs is a combination of Compound 3, Compound 4, and sofosbuvir; and themethod comprises administering 100 or 200 mg Compound 3 together with100 mg ritonavir once daily, 25 mg compound 4 once daily, and 400 mgsofosbuvir once daily; and the patient is an interferon non-responderinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient isinfected with HCV genotype 1. In still another example, the combinationof two or more DAAs is a combination of Compound 3, Compound 4, andsofosbuvir; and the method comprises administering 150 mg Compound 3together with 100 mg ritonavir once daily, 25 mg compound 4 once daily,and 400 mg sofosbuvir once daily; and the patient is a treatment-naïvepatient infected with HCV genotype 1. In still another example, thecombination of two or more DAAs is a combination of Compound 3, Compound4, and sofosbuvir; and the method comprises administering 150 mgCompound 3 together with 100 mg ritonavir once daily, 25 mg compound 4once daily, and 400 mg sofosbuvir once daily; and the patient is aninterferon non-responder infected with HCV genotype 1.

In any method described herein, the HCV polymerase inhibitor recitedtherein can be IDX21437 (a uridine nucleotide analog HCV NS5B polymeraseinhibitor, Idenix).

In any method described herein, the HCV polymerase inhibitor recitedtherein can also be IDX21459.

In any method described herein, the HCV NS5A inhibitor recited thereincan be GS-5816.

In any method described herein, the HCV NS5A inhibitor recited thereincan also be MK-8742.

In any method described herein, the patient being treated preferably isHCV genotype 1 patient.

It should be understood that the above-described embodiments and thefollowing examples are given by way of illustration, not limitation.Various changes and modifications within the scope of the presentinvention will become apparent to those skilled in the art from thepresent description.

Example 1. Clinical Modeling for Interferon-Free DAA CombinationTherapies

Treatment regimens comprising administration of Compound 1 and Compound2 were evaluated using clinical models described in U.S. PatentApplication Publication No. 2013/0102526, filed Oct. 19, 2012 andentitled “Methods for Treating HCV”, which is incorporated herein byreference in its entirety. These treatment regimens comprisedadministration of Compound 1 and Compound 2, but did not includeadministration of either interferon or ribavirin. Comparable SVR ratesare expected for interferon-non responders.

FIG. 1 shows the predicted median SVR percentages and 90% SVR confidenceintervals for 2-DAA regimens consisting of the use of Compound 1 (400 mgonce daily) and Compound 2 (120 mg once daily) to treat genotype 1 naïvesubjects. Different treatment durations were assessed. The predicted SVRrate for a 12-week treatment was about 95%. As used in all of thefigures of the present application, the vertical bar at the top of eachSVR percentage column represents the 90% SVR confidence interval, andthe x-axis (“Time (weeks)”) indicates the duration of each treatmentregimen.

FIG. 2 illustrates the predicted median SVR percentages and 90% SVRconfidence intervals for 2-DAA regimens consisting of the use ofCompound 1 (400 mg once daily) and Compound 2 (60 mg once daily) totreat genotype 1 naïve subjects. Different treatment durations wereassessed. The predicted SVR rate for a 12-week treatment was about85-90%.

FIG. 3 shows the predicted median SVR percentages and 90% SVR confidenceintervals for 2-DAA regimens consisting of the use of Compound 1 (600 mgonce daily) and Compound 2 (480 mg once daily) to treat genotype 1 naïvesubjects. Different treatment durations were assessed. The predicted SVRrate for a 12-week treatment was about 100%.

FIG. 4 depicts the predicted median SVR percentages and 90% SVRconfidence intervals for 2-DAA regimen consisting of the use of Compound1 (400 mg once daily) and Compound 2 (120 mg once daily) to treatgenotype 3 naïve subjects. Different treatment durations were assessed.The predicted SVR rate for a 12-week treatment was about 95%.

FIG. 5 illustrates the predicted median SVR percentages and 90% SVRconfidence intervals for 2-DAA regimen consisting of the use of Compound1 (400 mg once daily) and Compound 2 (60 mg once daily) to treatgenotype 3 naïve subjects. Different treatment durations were assessed.The predicted SVR rate of a 12-week treatment was about 85-90%.

FIG. 6 shows the predicted median SVR percentages and 90% SVR confidenceintervals for 2-DAA regimens consisting of the use of Compound 1 (600 mgonce daily) and Compound 2 (480 mg once daily) to treat genotype 3 naïvesubjects. Different treatment durations were assessed. The predicted SVRrate of a 12-week treatment was about 100%.

Treatment regimens comprising administration of Compound 1, Compound 2and sofosbuvir, or Compound 2 and sofosbuvir, were also evaluated usingthe same clinical model. FIG. 7 shows the predicted SVR for thetreatment regimen consisting of the use of Compound 1 (400 mg oncedaily), Compound 2 (120 mg once daily) and sofosbuvir (400 mg oncedaily) to treat genotype 1 naïve subjects. The treatment regimen did notinclude administration of either interferon or ribavirin. Differenttreatment durations were assessed. The predicted SVR rates of the2-week, 4-week, 6-week, 8-week, 10-week, and 12-week treatment regimenswere about 40%, 85%, 100%, 100%, 100%, and 100%, respectively.Comparable SVR rates are expected for interferon-non responders.

FIG. 8 shows the predicted SVR for the treatment regimen consisting ofthe use of Compound 2 (120 mg once daily) and sofosbuvir (400 mg oncedaily) to treat genotype 1 naïve subjects. The treatment regimen did notinclude administration of either interferon or ribavirin. Differenttreatment durations were assessed. The predicted SVR rates of the6-week, 8-week, 10-week, and 12-week treatment regimens were about 60%,95%, 100%, and 100%, respectively. Comparable SVR rates are expected forinterferon-non responders.

Example 2. Combination of Compound 1 and Compound 2 In Vitro

FIG. 9 shows that the combination of Compound 1 and Compound 2 exhibitssignificant synergistic effect on HCV inhibition as tested in HCV GT 1bCon-1 replication cells. The result was generated using Prichard andShipman model (Prichard et al. ANTIVIRAL RESEARCH 14:181-205 (1990)).

Compound 1 inhibited replication of HCV stable subgenomic repliconscontaining NS3 genes from GT 1a, 1b, 2a, 3a, 4a, or 6a with EC₅₀ valuesranging from 0.85 to 2.8 nM. Of note, Compound 1 was potent againstreplicon containing GT3a protease, with an EC₅₀ value of 1.6 nM.Compound 1 retained its activity against common GT1a and 1b variants atNS3 amino acid positions 155 and 168 that conferred resistance to otherHCV protease inhibitors (Pis). Resistant colony selection studies inGT1a and 1b subgenomic replicon cells identified A156T in GT1a and A156Vin GT1b as the most frequent variants, which conferred 1400- and1800-fold reduced susceptibility to Compound 1, respectively. However,these variants had in vitro replication capacities of only 1.5% and 9.2%that of their corresponding wild-type replicons. In a repliconcontaining GT3a NS3 protease, Compound 1 selected very few colonies atconcentrations ≧100-fold over its EC50 value. The colonies that survivedthe selection contained either A156G alone, or Q168R co-selected withY56H, which conferred 1500- or 1100-fold loss in susceptibility toCompound 1, respectively.

TABLE 2 Antiviral Activity of Compound 1 in the HCV Subgenomic StableReplicon Cell Culture Assay 0% Human Plasma^(a) Mean EC₅₀, nM, ±Std. HCVReplicon Subtype N^(b) Dev. Genotype 1a 9 0.85 ± 0.15 Genotype 1b 8 0.94± 0.35 Genotype 2a 2 2.7 ± 1.1 Genotype 3a 2  1.6 ± 0.49 Genotype 4a 4 2.8 ± 0.41 Genotype 6a 4 0.86 ± 0.11 ^(a)The 0% human plasma assaycontains 5% fetal bovine serum ^(b)Number of independent replicates

TABLE 3 Antiviral Activity of Compound 1 in the HCV Subgenomic StableReplicon Cell Culture Assay 40% Human Plasma^(a) Mean EC₅₀, nM, ±Std.HCV Replicon Subtype N^(b) Dev. Genotype 1a 10 5.3 ± 1.0 Genotype 1b 8 10 ± 5.0 ^(a)The 0% human plasma assay contains 5% fetal bovine serum^(b)Number of independent replicates

When tested against common HCV genotype 1 NS3 resistance-associatedvariants, such as V36M, R155K, D168A and D168V in GT 1a (H77), or T54A,R155K, D168V and V170A in GT 1b (Con-1), Compound 1 showed inhibitoryactivity nearly equivalent to that against wild-type HCV replicon.Compound 1 was also shown to have potent activity against many NS5Ainhibitor and NS5B inhibitor resistance-associated variants in vitro(e.g., M28T, M28V, Q30D, Q30R, Y93C, Y93H, Y93N, L31V+Y93H, C316Y,M414T, Y448C, Y448H, S556G and S559G in GT 1a, and L28T, Y93H, S282T,C316Y, Y448H and S556G in GT 1b).

Example 3. High SVR in HCV Genotype 1 (GT1) Non-CirrhoticTreatment-Naïve Patients or Pegylated Interferon/Ribavirin NullResponders Treated with the Combination of Compound 1 and Compound 2

Compound 1 and Compound 2 are characterized by potent pangenotypic invitro antiviral activity against major HCV genotypes (GTs), includingactivity against key known resistance-associated variants and a highbarrier to resistance selection. Monotherapy with Compound 1 or Compound2 resulted in a mean 4 log₁₀ IU/mL decline from baseline in HCV plasmaviral load in GT1-infected subjects with and without compensatedcirrhosis.

In this phase 2 study, treatment with Compound 1 and Compound 2 for 12weeks is evaluated in HCV GT1-infected subjects without cirrhosis.Non-cirrhotic GT1-infected treatment-naïve (TN) or pegylatedinterferon/ribavirin (pegIFN/RBV) null responder subjects receivedonce-daily Compound 1 200 mg+Compound 2 120 or 40 mg for 12 weeks, andsubsequently were followed for 24 weeks. Efficacy was measured bysustained virologic response after the last dose of study drug (SVR).Safety was evaluated by adverse event (AE) monitoring, laboratorytesting, and other standard assessments.

79 subjects (male, 52%; median [range] age, 54.0 [26.0-70.0] years;GT1a, 81%; GT1b, 19%; TN, 63%; pegIFN/RBV null responders, 37%;fibrosis >F2, 25%; median [range] HCV RNA log₁₀ IU/mL, 6.8 [4.4-7.5])were enrolled, 40 received Compound 1 200 mg+Compound 2 120 mg, and 39received Compound 1 200 mg and Compound 2 40 mg. SVR 4 weeks after thelast dose of study drug (SVR4) was achieved in 29 of 29 (100%)pegIFN/RBV null responders and 49 of 50 (98%) TN subjects. There were notreatment-related serious AEs or clinically relevant laboratoryfindings. The most common AEs (reported in >5% of subjects) werefatigue, headache, nausea, diarrhea, and anxiety.

Once-daily 12-week treatment with the combination of Compound 1 andCompound 2 of GT1 infection in non-cirrhotic TN and pegIFN/RBV nullresponders resulted in high SVR4 (98%-100%) rates. One treatment relapsewas observed.

Non-cirrhotic HCV GT1-infected patients treated with the combination ofCompound 1 and Compound 2 for 12 weeks achieved high SVR12 rates,regardless of prior treatment experience or presence of baselinevariants.

Treatment with the combination of Compound 1 and Compound 2 for 12 weeksis also expected to achieve high SVR in GT1 subjects with compensatedcirrhosis. Likewise, high SVR is expected in GT1 patients if treatedwith the combination of Compound 1 and Compound 2 once-daily for only 8weeks. Suitable dosing includes, but is not limited to, Compound 1 300mg+Compound 2 120 mg once daily, or Compound 1 200 mg+Compound 2 80 mgonce daily.

Example 4. High SVR Achieved with Compound 1 and Compound 2 inNon-Cirrhotic Treatment-Naïve and Treatment-Experienced Patients withHCV Genotype 2 (GT2) Infection

As shown in Example 3, Compound 1 and Compound 2 are potent inhibitorsagainst GT1. Compound 1 and Compound 2 have comparable in vitroantiviral potency against GT2. This Example evaluates the efficacy andsafety of Compound 1 and Compound 2 with or without ribavirin (RBV) innon-cirrhotic GT2-infected treatment-naïve (TN) and pegylatedinterferon/RBV (pegIFN/RBV) treatment experienced (TE) subjects.

Subjects received 12 weeks of Compound 1 300 mg+Compound 2 120 mg (ArmA), Compound 1 200 mg+Compound 2 120 mg (Arm B), or Compound 1 200mg+Compound 2 120 mg+RBV (Arm C). DAAs were dosed once daily;weight-based RBV (1000 or 1200 mg) was dosed twice daily. Subjects werethen followed for 24 weeks. Efficacy was measured by sustained virologicresponse after the last dose of study drug (SVR). Safety was evaluatedby monitoring adverse events (AEs), laboratory tests, and vital signs.

75 subjects were treated in Arms A-C(n=25 each); 74 had GT2, and 1subject initially randomized to Arm B was determined to have GT3ainfection. Subjects were male, 63%; median (range) age, 57.0 (20.0-69.0)years; GT2b, 81%; TN, 88%; TE, 12%; F0-F2, 87%; F3, 13%; median (range)baseline HCV RNA log₁₀ IU/mL, 7.1 (4.7-7.8). No subjects haveexperienced virologic failure. One subject in Arm A prematurelydiscontinued study drugs and was lost to follow-up. The SVR4 rates (ITTanalysis) are 96% (24/25), 100% (24/24), and 100% (25/25) in Arms A, B,and C, respectively. Most AEs were mild, with the most commonDAA-related AEs being fatigue, nausea, headache, and diarrhea. Therewere no serious DAA-related AEs. Typical reductions in hemoglobin wereobserved in the RBV-containing arm.

Compound 1+Compound 2 with or without RBV for 12 weeks was highlyeffective and well tolerated, achieving SVR4 rates of 96%-100%.

The once daily regimen of the combination of Compound 1 and Compound 2was well tolerated and demonstrated high SVR12 rates, regardless ofprior treatment experience or presence of baseline variants innon-cirrhotic patients with GT2 infection.

Treatment with the combination of Compound 1 and Compound 2 for 12 weeksis also expected to achieve high SVR in GT2 subjects with compensatedcirrhosis. Likewise, high SVR is expected in GT2 patients if treatedwith the combination of Compound 1 and Compound 2 once-daily for only 8weeks. Suitable dosing includes, but is not limited to, Compound 1 300mg+Compound 2 120 mg once daily, or Compound 1 200 mg+Compound 2 80 mgonce daily.

Example 5. High SVR Achieved with Compound 1 and Compound 2 inNon-Cirrhotic Treatment-Naïve and Treatment-Experienced Patients withHCV Genotype 3 (GT3) Infection

As shown in Example 3, Compound 1 and Compound 2 are potent inhibitorsagainst GT1. Compound 1 and Compound 2 have comparable in vitroantiviral potency against GT3. This Example evaluates the efficacy andsafety of Compound 1 and Compound 2 with or without ribavirin (RBV) innon-cirrhotic GT3-infected treatment-naïve (TN) and pegylatedinterferon/RBV (pegIFN/RBV) treatment experienced (TE) subjects.

Subjects received 12 weeks of Compound 1 300 mg+Compound 2 120 mg (ArmD), Compound 1 200 mg+Compound 2 120 mg (Arm E), Compound 1 200mg+Compound 2 120 mg+RBV (Arm F), or Compound 1 200 mg+Compound 2 40 mg(Arm G). DAAs were dosed once daily; weight-based RBV (1000 or 1200 mg)was dosed twice daily. Efficacy was measured by sustained virologicresponse after the last dose of study drug (SVR). Safety was evaluatedby monitoring adverse events (AEs), laboratory tests, and vital signs.

120 GT3-infected subjects were treated in Arms D (n=30), E (n=29), F(n=31), or G (n=30). Subjects were male, 56%; median age, 52.0 years;GT3a, 98%; TN, 92%; TE, 8%; fibrosis >F2, 15%; median baseline HCV RNAlog₁₀ IU/mL, 6.7. There has been 1 virologic failure in each treatmentarm (n=4), 3 of which were in pegIFN/RBV TE subjects. One subject in ArmG was lost to follow-up at the week 2 visit. The SVR4 rate was 96%(27/28), 96% (27/28), 97% (29/30) and 93% (27/29) in Arms D, E, F, andG, respectively. AEs were mostly mild, with most common DAA-related AEsbeing fatigue, nausea, and headache. There were no serious DAA-relatedAEs; 1 subject discontinued due to DAA- and RBV-related AEs of abdominalpain and heat sensation. Typical reductions in hemoglobin were observedin the RBV containing arm (Arm F).

Compound 1+Compound 2 treatment for 12 weeks with or without RBV in TNor TE non-cirrhotic HCV GT3-infected subjects was well tolerated.Promising SVR4 rates of 93%-96% were achieved without RBV. Furthertesting showed that Arms D, E, F and G achieved 93%, 93%, 94% and 83%SVR12, respectively.

Treatment with the combination of Compound 1 and Compound 2 for 12 weeksis also expected to achieve high SVR in GT3 subjects with cirrhosis.Likewise, high SVR is expected in GT3 patients if treated with thecombination of Compound 1 and Compound 2 once-daily for only 8 weeks.Suitable dosing includes, but is not limited to, Compound 1 300mg+Compound 2 120 mg once daily, or Compound 1 200 mg+Compound 2 80 mgonce daily.

Example 6. Drug-Drug Interactions Between Compound 1 and Compound 2 withCyclosporine or Tacrolimus in Healthy Subjects

Compound 1+Compound 2 combination demonstrated high sustained virologicresponse rate in Phase 2 studies. Two Phase 1, open-label studies wereconducted to assess the pharmacokinetics, safety and tolerability whenCompound 1+Compound 2 is coadministered with immunosuppressantscyclosporine or tacrolimus.

Healthy adults subjects received single doses of cyclosporine 100 mg(n=12) or tacrolimus 1 mg (n=12) alone or in combination with Compound 1300 mg QD (i.e., once daily)+Compound 2 120 mg QD. Intensive bloodsampling for determination of cyclosporine, tacrolimus, Compound 1 andCompound 2 concentrations was performed and pharmacokinetic parameters(maximum observed concentration [C_(max)], area under theconcentration-time curve [AUC_(t) or AUC_(inf)] and trough concentration[C₂₄]) were estimated. Safety and tolerability were assessed throughoutthe study.

Cyclosporine C_(max), AUC_(t), and AUC_(inf) in blood were minimallyaffected (≦14% change) when coadministered with steady-state Compound1+Compound 2. Steady-state C_(max), AUC₂₄, and C₂₄ in plasma wereslightly increased for Compound 1 (30%, 37%, and 34%, respectively) andfor Compound 2 (11%, 22%, and 26%, respectively) when coadministeredwith cyclosporine. Tacrolimus C_(max), AUC_(t), and AUC_(inf) in bloodwere slightly increased (50%, 53%, and 45%, respectively) whencoadministered with steady-state Compound 1+Compound 2. Steady-stateC_(max), AUC₂₄, and C₂₄ in plasma were minimally affected for Compound 1(≦11% change) and for Compound 2 (≦2% change) when coadministered withtacrolimus.

No serious adverse events were observed in either study. There were nopatterns to the adverse events reported, and no new safety issues wereidentified.

No dose adjustment should be required for Compound 1, Compound 2, andcyclosporine when coadministered. No dose adjustment should be requiredfor Compound 1 and Compound 2 when coadministered with tacrolimus. Itmay be considered that subjects receiving tacrolimus should continue touse their current dose when initiating treatment with DAAs, and reducethe dose of tacrolimus if necessary based on therapeutic monitoring.

Example 7. Absence of Significant Drug-Drug Interactions BetweenCompound 1/Compound 2 and Methadone or Buprenorphine/Naloxone inSubjects on Opioid Maintenance Therapy

A Phase 1, open-label study was conducted to assess thepharmacokinetics, safety and tolerability of Compound 1+Compound 2 andmethadone or buprenorphine/naloxone. Otherwise healthy adults subjectson individualized regimens of methadone (n=12) or buprenorphine/naloxone(n=12) for opioid addiction received Compound 1 300 mg QD+Compound 2 120mg QD for 7 days. Intensive blood sampling for determination ofmethadone, buprenorphine, norbuprenorphine, naloxone, Compound 1 andCompound 2 concentrations was performed and pharmacokinetic parameters(maximum observed concentration [C_(max)], area under theconcentration-time curve [AUC₂₄ or AUC_(t)] and trough concentration[C₂₄]) were estimated. Safety and tolerability were assessed throughoutthe study. Potential opioid withdrawal or overdose symptoms(pharmacodynamics) were assessed with validated instruments includingthe short opiate withdrawal scale, desire for drugs questionnaire, andpupillometry measurements throughout the study.

For subjects on methadone maintenance therapy, dose-normalized C_(max),AUC₂₄, and C₂₄ for R- and S-methadone were unaffected bycoadministration with Compound 1 and Compound 2 at steady-state (≦5%change). For subjects on buprenorphine/naloxone maintenance therapy,dose-normalized C_(max), AUC₂₄, and C₂₄ were slightly increased forbuprenorphine (8%, 17%, and 24%, respectively) and norbuprenorphine(25%, 30%, and 21%, respectively) when coadministered with Compound 1and Compound 2 at steady-state; naloxone dose-normalized C_(max) andAUC_(t) were minimally affected (≦12% change). Pharmacodynamics of themethadone or buprenorphine/naloxone regimens were not significantlyimpacted by coadministration with Compound 1 or Compound 2 for eitherregimen. Compound 1 and Compound 2 exposures following coadministrationwith methadone or buprenorphine/naloxone were similar to the observedvalues in previous studies.

Subjects experienced adverse events of mild intensity, with the mostcommon (reported in >5 subjects) being abdominal pain, constipation, andheadache; all subjects completed the study. There were no clinicallyrelevant abnormal laboratory abnormalities, ECG or vital sign findings.

No dose adjustments should be required for coadministration of Compound1 and Compound 2 with methadone or buprenorphine/naloxone. Nopharmacodynamic interaction is expected.

Example 8. Pharmacokinetics of Coadministration of Pan-Genotypic, DirectActing Antiviral Agents, Compound 1 and Compound 2, with or withoutRibavirin for 12 Weeks in HCV Infected Subjects without Cirrhosis

Pharmacokinetics of Compound 1 and Compound 2 with or without ribavirin(RBV) were evaluated. Two open-label, multicenter studies were conductedto evaluate the efficacy, safety, and pharmacokinetics ofco-administration of Compound 1 (200 or 300 mg QD) and Compound 2 (40 or120 mg QD) with or without RBV in GT1-, GT2- or GT3-infected subjects.Blood samples for pharmacokinetic analysis were collected throughout thestudy treatment period. Compound 1 and Compound 2 pharmacokineticsfollowing a single dose (Day 1) and at steady state (Week 4) wereassessed by non-compartmental methods.

A total of 274 subjects received Compound 1 and Compound 2 with orwithout RBV. Both Compound 1 and Compound 2 showed rapid absorption withTmax ranging from 2 to 4 hours. Steady state Compound 1 exposure (areaunder the curve from 0 to 4 hour) following 300 mg was 2570 ng·h/mL,approximately 3.7-fold of the exposure following 200 mg administration.Coadministration of either 40 mg or 120 mg Compound 2 each with 200 mgCompound 1 resulted in Compound 2 exposure of 157 or 372 ng·h/mL,respectively. Compound 1 300 mg increased 120 mg Compound 2 exposure byan additional 20% to 30%. Minimal accumulation in Compound 1 or Compound2 exposure was observed at Week 4 compared to Day 1. Compound 2 hadminimal impact on Compound 1 exposures, however, Compound 1 200 mg and300 mg increased 120 mg Compound 2 exposures to 3- to 4-fold of Compound2 exposures when administered alone. HCV genotype and RBVcoadministration had no impact on Compound 1 or Compound 2 exposures.

Compound 1 exhibited non-linear pharmacokinetics with more thandose-proportional increase in exposures with increasing doses, whileCompound 2 exposures increased in an approximately dose-proportionalmanner when coadministered with Compound 1. Compound 2 had minimalimpact on Compound 1, while Compound 1 increased Compound 2 exposures,with the increase in Compound 2 exposure being dependent on Compound 1dose. Compound 1 or Compound 2 had minimal accumulation in exposuresfollowing multiple dosing in HCV-infected subjects.

Example 9. Drug-Drug Interactions Between Compound 1/Compound 2 andSofosbuvir

A Phase 1 study was conducted to evaluate any potential interactionsduring co-administration of Compound 1+Compound 2 with sofosbuvir. Thiswas an open label, randomized, multiple-dose, non-fasting study in 16healthy subjects who were assigned 1:1 to one of two cohorts to receiveeither Compound 1 400 mg QD+Compound 2 120 mg QD or sofosbuvir 400 mg QDfor 7 days (Period 1), followed by the combination of Compound 1 400 mgQD+Compound 2 120 mg QD with sofosbuvir 400 mg QD for 7 additional days(Period 2). Intensive pharmacokinetic assessments were performed onStudy Days 1 and 7 in each period. Pharmacokinetic interaction betweenCompound 1+Compound 2 and sofosbuvir were assessed by arepeated-measures analysis using SAS. Safety was evaluated throughassessment of adverse events, vital signs, ECGs and clinical laboratorytests.

Coadministration with steady-state Compound 1 and Compound 2 increasedsofosbuvir C_(max) and AUC₂₄ by 66% and 125%, respectively; C_(max) andAUC₂₄ for the major circulating sofosbuvir metabolite GS-331007 wereminimally affected (≦21% difference) and C₂₄ was increased by 85%.Compound 1 and Compound 2 exposures were minimally affected bysofosbuvir (≦16% difference). There were no patterns to the adverseevents reported, and no new safety issues were identified.

This study showed that no dose adjustments are needed forcoadministration of Compound 1 and Compound 2 with sofosbuvir.

Example 10. Pharmacokinetics, Tolerability and Safety of Compound 2Following Single and Multiple Doses in Healthy Subjects

The study's objectives were to determine the pharmacokinetics (PK),safety, and tolerability of Compound 2 following single ascending doses(SAD) and multiple ascending doses (MAD) and effect of food on Compound2 PK in healthy adults. This was a blinded, randomized,placebo-controlled Phase 1 study. Seven Compound 2 doses ranging from1.5 mg to 600 mg were evaluated in the SAD portion (n=53, 3:1 active toplacebo ratio). Compound 2 doses of 30 mg to 600 mg QD were evaluated inMAD portion for 10 days (n=39, 4:1 active to placebo ratio). The effectof food on Compound 2 120 mg was assessed in a crossover fashion in 12healthy subjects. The PK parameters of Compound 2 were estimated usingnon-compartmental methods. Safety and tolerability were assessedthroughout the study.

Compound 2 exposures increased in a greater than dose proportionalmanner across the 1.5 mg to 120 mg dose range, while PK was linearacross the 120 mg to 600 mg dose range. Compound 2 plasma concentrationreached T_(max) at 3 to 5 hours. Following Compound 2 QD dosing for 10days, the Compound 2 steady state exposures were 53% higher compared toexposures after the first dose. Compound 2 half-lives ranged from 20 to22 hours. Steady state of Compound 2 was attained by Study Day 5. Foodhad minimal effect on the bioavailability of Compound 2 (<14%). Alladverse events were assessed as mild. No clinically significant vitalsigns or laboratory measurements were observed during the course of thestudy.

This study showed that Compound 2 PK support QD dosing andadministration without regard to food. All dose levels were welltolerated and a maximum tolerated dose was not reached in the SAD andMAD portions of the study.

Example 11. High SVR in HCV Genotype 1 Non-Cirrhotic Treatment-Naïve or-Experienced Patients with the Combination of Compound 1 and Compound 2for 8 Weeks

Compound 1 and Compound 2 co-administered for 12 weeks showed highsustained virologic response (SVR) rates and was well tolerated innon-cirrhotic patients with HCV genotype 1 (GT1) infection. This Exampleshows the efficacy and safety data of the combination of Compound 1 andCompound 2 administered for 8 weeks in non-cirrhotic patients with GT1infection.

Treatment-naïve or pegylated interferon treatment-experienced patientsreceived once-daily Compound 1 300 mg+Compound 2 120 mg for 8 weeks. SVRat post-treatment week 4 (SVR₄; HCV RNA measured using COBAS TaqMan®RT-PCR [lower limit of detection of 15 IU/mL and lower limit ofquantitation of 25 IU/mL]) and safety data were determined.

34 patients were enrolled: 56% male, 97% white, 71% GT1a, 68% non-CCIL28B, 15% had an F3 fibrosis stage at baseline, and 15% were treatmentexperienced. The median (range) HCV RNA log₁₀ IU/mL was 6.5 (2.9-7.5) atbaseline, and 38% of patients had HCV RNA ≧6,000,000 IU/mL. After 8-weektreatment, all 34 (100%) patients achieved SVR₄ and 97% of the patientsachieved SVR12. One patient did not achieve SVR12 after achieving SVR4due to death from advanced cancer not related to study drugs. There wereno additional serious or severe AEs reported. The most frequent AEsobserved in >10% of patients were fatigue (21%) and diarrhea (12%).

This study showed that the combination of Compound 1 and Compound 2 waswell tolerated and achieved high SVR rate in all treatment-naïve or-experienced patients with GT1 infection who completed 8 weeks oftreatment, regardless of baseline viral load, baseline viral load, priortreatment history, or presence of baseline NS3 and/or NS5A variants.

Example 12. High SVR Rates with the Combination of Compound 1+Compound 2for 8 Weeks in Non-Cirrhotic Patients with HCV Genotype 2 Infection

Compound 1+Compound 2 for 12 weeks was well tolerated and achievedsustained virologic response (SVR) rates between 97-100% innon-cirrhotic patients with HCV genotype (GT) 1 or 2 infection. In thisExample, Compound 1+Compound 2 was co-administered to HCV GT2 patientsfor a shorter duration of 8 weeks.

Non-cirrhotic treatment-naïve patients or pegylated interferon/ribavirintreatment-experienced non-responders received once-daily Compound 1 300mg+Compound 2 120 mg for 8 weeks. HCV RNA <25 IU/mL at post-treatmentweeks 4 (SVR4) and safety were evaluated.

54 patients with GT2 infection (70% GT2b; 59% non-CC IL28B genotype; 13%treatment-experienced) were enrolled, respectively. Mean baseline HCVRNA log₁₀ IU/mL±standard deviation was 6.6±0.8 for these GT2-infectedpatients, with 57% of patients who had baseline levels ≧6M IU/mL. SVR4was achieved by 98% (53/54) of GT2-infected patients. The GT2-infectedpatient without SVR4 was lost to follow up after week 6, where HCV RNAwas not detected. There were no other discontinuations due to AEs. AEswere mostly mild (Grade 1), with the most common AEs being fatigue andheadache.

This study showed that the combination of Compound 1 and Compound 2administered for 8 weeks in non-cirrhotic patients with HCV GT2infection was well tolerated and achieved high SVR, regardless ofbaseline viral load or prior treatment history.

Example 13. High SVR Rates with Compound 1+Compound 2 Co-Administeredfor 8 Weeks in Non-Cirrhotic Patients with HCV Genotype 3 Infection

Treatment-naïve HCV GT3-infected patients without cirrhosis receivedonce-daily Compound 1 300 mg+Compound 2 120 mg for 8 weeks. SVR4 (HCVRNA below the lower limit of quantitation [25 IU/mL] at post-treatmentweek 4) and safety were assessed.

29 patients were enrolled: 52% male, 90% white, 86% GT3a, and 62% non-CCIL28B. The median (range) HCV RNA log₁₀ IU/mL was 6.3 (5.0-7.5) and 24%of patients had HCV RNA ≧6M IU/mL at baseline. SVR4 was achieved by 97%(28/29) of patients. No patients experienced virologic failure to date.One patient discontinued the study after treatment week 6 (HCV RNAundetectable at this visit) due to intolerance of blood draws. Nopatients discontinued due to adverse events (AEs) or experienced seriousAEs. The majority of AEs were mild in severity, with the most common AEs(>10% of patients) reported for patients being headache and fatigue.

This study showed that the combination of Compound 1 and Compound 2,co-administered for 8 weeks in treatment-naïve, non-cirrhotic patientswith HCV GT3 infection was well-tolerated and achieved high SVR rates.

Example 14. Antiviral Activity of Compound 2 in Combination withParitaprevir/Ritonavir and Ribavirin Against Hepatitis C Virus Genotype3 Infection

Efficacy, pharmacokinetics, and safety of Compound 2 co-administeredwith paritaprevir/ritonavir and ribavirin were evaluated in this phase2, open-label, multicenter study in treatment-naïve non-cirrhoticpatients with HCV genotype 3 infection. Ten patients, all genotype 3a,received 120 mg Compound 2 and 150/100 mg paritaprevir/ritonavir oncedaily with weight-based ribavirin for 12 weeks. A total daily dose of1000 mg ribavirin if the patient's body weight was <75 kg or 1200 mg ifbody weight was ≧75 kg was divided twice daily (BID).

Nine (90%) patients achieved sustained virologic response atpost-treatment weeks 12 and 24. One patient experienced virologicfailure at treatment week 6. Sequence analyses for HCV variants insamples from this patient identified A166S in NS3 at baseline and afterbreakthrough, as well as A30K at baseline and linked S24F+M28K+A30Kvariants in NS5A after breakthrough. Neither NS3 A166S nor NS5A A30Kvariant confers any resistance to paritaprevir or Compound 2,respectively. However, NS5A S24F+M28K+A30K linked variant confersa >5000-fold increase in Compound 2 EC₅₀ relative to that of thewild-type replicon. This patient's Compound 2 exposure was comparable tothe cohort, while paritaprevir and ritonavir exposures were the lowestof all patients. No serious or severe adverse events and adverse eventsleading to early discontinuation were reported.

The study confirmed that Compound 2 in combination withparitaprevir/ritonavir and ribavirin is effective against HCV genotype 3infection.

Example 15. 100% SVR4 and Favorable Safety of Compound 1+Compound 2Administered for 12 Weeks in Non-Cirrhotic Patients with Genotypes 4, 5,or 6 Infection

This study evaluated the efficacy and safety of Compound 1 and Compound2 co-administered for 12 weeks in non-cirrhotic patients with HCVgenotypes 4, 5, or 6 infection. Treatment-naïve or pegylatedinterferon/ribavirin treatment-experienced patients received once-dailyCompound 1 300 mg+Compound 2 120 mg for 12 weeks. Sustained virologicresponse at post-treatment week 4 (SVR4; HCV RNA measured using COBASTaqMan® RT-PCR [lower limit of detection of 15 IU/mL and lower limit ofquantitation of 25 IU/mL]) and safety data was assessed.

A total of 34 patients with genotype 4 (n=22; 65%), 5 (n=1; 3%), or 6(n=11; 32%) infection were enrolled: 53% male, 59% white, 62% had non-CCIL28B, and 15% were treatment-experienced. The median (range) HCV RNAlog₁₀ IU/mL was 6.4 (4.6-7.4) at baseline, and 35% of patients had HCVRNA ≧6,000,000 IU/mL. SVR4 was achieved by all 34 (100%) patients withgenotypes 4, 5, or 6 infection. Adverse events (AEs) reported weredeemed mostly Grade 1 (mild) in severity, with common AEs in >5% of allpatients being headache (24%), diarrhea (15%), fatigue (12%), nausea(9%), arthralgia (6%), dizziness (6%), dry mouth (6%), and flatulence(6%). No severe AEs, serious AEs, premature discontinuations due to AEswere reported. While receiving therapy, no liver function or otherlaboratory abnormalities were observed.

This study showed that the combination of Compound 1 and Compound 2 waswell tolerated and demonstrated 100% SVR4 in non-cirrhotic patients withgenotype 4, 5, or 6 infection. These results along with previouslyreported promising efficacy in GT1, 2, and 3 infection establish potentclinical pangenotypic activity of this RBV-free once daily Compound1+Compound 2 regimen.

Example 16. High Efficacy and Favorable Safety of Compound 1 andCompound 2 Co-Administration for 12 Weeks in HCV Genotype 1-InfectedPatients with Cirrhosis

This study evaluated the safety and efficacy of Compound 1 and Compound2 administered for 12 weeks in HCV GT1-infected patients withcompensated cirrhosis. Treatment-naïve or pegylated interferon/ribavirintreatment-experienced patients received Compound 1 200 mg+Compound 2 120mg once daily for 12 weeks. Cirrhosis was determined by either liverbiopsy (Metavir F4), Fibroscan (liver stiffness >14.6 KPa) or serummarkers (Fibrotest score ≧0.75 and an APRI >2). SVR at post-treatmentweek 12 (SVR12; HCV RNA levels determined using Roche COBAS TaqMan®RT-PCR assay [lower limit of detection of 15 IU/mL and lower limit ofquantification of 25 IU/mL]) and safety were assessed.

A total of 27 patients were enrolled and the population was 74% male,89% white, 74% GT1a, 85% non-CC IL28B, 26% HCV treatment-experienced,and all reported fibrosis scores of F4 at baseline (1 missing). Themedian (range) HCV RNA log₁₀ IU/mL was 6.7 (5.6-7.3), and 93% had HCVRNA ≧6,000,000 IU/mL at baseline. Efficacy data shows 26 out of 27 (96%)of patients achieved SVR12, with one patient experiencing relapse atpost-treatment week 4. Most adverse events (AEs) were deemed Grade 1(mild) or Grade 2 (moderate) in severity, with no patients reportingsevere or serious AEs considered related to study drugs. No patientsdiscontinued treatment prematurely due to AEs and the most frequent AEsreported in >10% of patients were fatigue (11%) and headache (11%).While on-treatment, no clinically meaningful abnormal liver function orother laboratory results were observed.

The study showed that treatment with the IFN- and ribavirin-freecombination of Compound 1 and Compound 2 was well-tolerated and achievedhigh SVR12 rates of 96% following a 12-week treatment regimen inGT1-infected patients with compensated cirrhosis regardless of baselineviral load or prior treatment history.

The foregoing description of the present invention provides illustrationand description, but is not intended to be exhaustive or to limit theinvention to the precise one disclosed. Modifications and variations arepossible in light of the above teachings or may be acquired frompractice of the invention. Thus, it is noted that the scope of theinvention is defined by the claims and their equivalents.

What is claimed is:
 1. A method of treatment for hepatitis C virus (HCV)infection, comprising administering 200-600 mg Compound 1 or apharmaceutically acceptable salt thereof once daily, and 100-500 mgCompound 2 or a pharmaceutically acceptable salt thereof once daily, toa patient infected with HCV, wherein said treatment does not includeadministration of either interferon or ribavirin to said patient, andsaid treatment lasts for 8 or 12 weeks.
 2. The method of claim 1,wherein said treatment lasts for 12 weeks.
 3. The method of claim 1,wherein said treatment lasts for 8 weeks.
 4. The method of claim 1,wherein said patient is administered with 300 mg Compound 1 once dailyand 120 mg Compound 2 once daily.
 5. The method of claim 4, wherein saidpatient is without cirrhosis.
 6. The method of claim 4, wherein saidpatient is with compensated cirrhosis.
 7. The method of claim 4, whereinsaid patient is infected with HCV genotype
 1. 8. The method of claim 4,wherein said patient is infected with HCV genotype
 2. 9. The method ofclaim 4, wherein said patient is infected with HCV genotype
 3. 10. Themethod of claim 4, wherein said patient is infected with HCV genotype 4.11. The method of claim 4, wherein said patient is infected with HCVgenotype
 5. 12. The method of claim 4, wherein said patient is infectedwith HCV genotype
 6. 13. A method of treatment for HCV infection,comprising administering 200-600 mg Compound 1 or a pharmaceuticallyacceptable salt thereof once daily, and 100-500 mg Compound 2 or apharmaceutically acceptable salt thereof once daily, to a patientinfected with HCV, wherein said treatment does not includeadministration of either interferon or ribavirin to said patient, andsaid treatment lasts for 16 weeks.
 14. The method of claim 13, whereinsaid patient is administered with 300 mg Compound 1 once daily and 120mg Compound 2 once daily.
 15. The method of claim 14, wherein saidpatient is infected with HCV genotype
 1. 16. The method of claim 14,wherein said patient is infected with HCV genotype
 2. 17. The method ofclaim 14, wherein said patient is infected with HCV genotype
 3. 18. Themethod of claim 14, wherein said patient is infected with HCV genotype4.
 19. The method of claim 14, wherein said patient is infected with HCVgenotype
 5. 20. The method of claim 14, wherein said patient is infectedwith HCV genotype 6.